Respiratory system Flashcards
Asthma DR
D: A chronic inflammatory disease of the respiratory system characterized by bronchial hyperresponsiveness, episodic exacerbation (asthma attacks), and reversible airflow obstruction. Manifests with reversible cough, wheezing, and dyspnea.
R: The exact etiology of asthma remains unknown. Known risk factors for asthma include the following:
Family history of asthma
Past history of allergies
Atopic dermatitis
Low socioeconomic status.
Childhood exposure to second-hand smoke increases the risk of developing asthma.
personal or family history of atopy
antenatal factors: maternal smoking, viral infection during pregnancy (especially RSV)
low birth weight
not being breastfed
maternal smoking around child
exposure to high concentrations of allergens (e.g. house dust mite)
air pollution. occupation.
‘hygiene hypothesis’: studies show an increased risk of asthma and other allergic conditions in developed countries. Reduced exposure to infectious agents in childhood prevents normal development of the immune system resulting in a Th2 predominant response.
Focusing on atopy, patients with asthma also suffer from other IgE-mediated atopic conditions such as: atopic dermatitis (eczema) allergic rhinitis (hay fever)
Asthma DEAC
Differential diagnosis of chronic cough:
In adults: Upper airway cough syndrome (chronic rhinitis, chronic sinusitis, vasomotor rhinitis), asthma, gastroesophageal reflux disease (GERD), chronic bronchitis, ACE-inhibitor-induced cough.
lESS COMMON in adults: emphysema, bronchiectasis, lung cancer, cystic fibrosis.
In children: infants: congenital defects (oesophageal atresia with/without tracheoesophageal fistula, vascular rings), foreign body aspiration.
Older children, upper respiratory tract infection, GERD, pertussis, viral bronchitis, cystic fibrosis, immune deficiency disorders. Dyspnea. COPD.
COPD: typically > 40 years old, cigarette consumption (90% of cases), insidious onset and chronic progression over years. Persistent airflow limitation, good response to parasympatholytics (e.g, ipratropium bromide).
Asthma: often childhood or adolescence, although nonallergic asthma can manifest after the age of 40, allergic and nonallergic, episodic: symptom-free phases, sudden attacks. Reversible, good response to treatment with long term inhaled corticosteroids.
E: Prevalence 5–10% of the US population More common in black than white patients For unknown reasons, the prevalence of asthma has been increasing over the past 20 years. [1] Sex: differs depending on age at onset ♂ > ♀ in patients < 18 years ♀ > ♂ in patients > 18 years Age of onset Allergic asthma: typically in childhood Nonallergic asthma: typically > 40 years
A:The exact etiology of asthma remains unknown. Known risk factors for asthma include the following:
Family history of asthma
Past history of allergies
Atopic dermatitis
Low socioeconomic status.
The following factors can also act as initial triggers of asthma or exacerbate an existing condition:
Allergic asthma (extrinsic asthma)
Cardinal risk factor: atopy
Environmental allergens: pollen (seasonal), dust mites, domestic animals , mold spores
Allergic occupational asthma: from exposure to allergens in the workplace (e.g., flour dust)
Nonallergic asthma (intrinsic asthma)
Viral respiratory tract infections (one of the most common stimuli, especially in children) [4]
Cold air
Physical exertion (exercise-induced asthma)
Gastroesophageal reflux disease (GERD): often exists concurrently with asthma
Chronic sinusitis or rhinitis
Medication: aspirin/NSAIDS (aspirin-induced asthma), beta-blockers
Stress
Irritant-induced asthma (e.g., from exposure to solvents, ozone, tobacco or wood smoke, cleaning agents).
C: Mild to moderate signs and symptoms
Persistent, dry cough that worsens at night, with exercise, or on exposure to triggers/irritants (e.g., cold air, allergens, smoke)
End-expiratory wheezes
Dyspnea
Chest tightness
Chronic allergic rhinitis with nasal congestion
Severe signs and symptoms
Severe dyspnea
Pulsus paradoxus
Hypoxemia
Accessory muscle use
Increased risk of pulmonary infection (in chronic asthma)
Cough variant asthma
A form of asthma in which the predominant symptom is chronic, dry cough
Other characteristic symptoms of asthma (e.g., wheezes, congestion, dyspnea) are absent.
Characteristic examination findings may not be present between episodes of asthma exacerbation!
Clinical examination
Auscultation (characteristic findings are usually only present during acute attacks)
Prolonged expiratory phase with wheezing (dry crackles)
Decreased breath sounds; possibly “silent chest”
Tachypnea
Percussion
Hyperresonant sound
Inferior displacement and poor movement of the diaphragm
In severe attacks
Altered level of consciousness
Cyanosis
asthma-PIMP
P: Asthma is generally characterized as an inflammatory disease driven by T-helper type 2 (Th2-cell) that manifests in individuals with a genetic predisposition. It consists of the following three pathophysiologic processes:
Bronchial hyperresponsiveness
Bronchial inflammation
Symptoms are primarily caused by inflammation of the terminal bronchioles, which are lined with smooth muscle but lack the cartilage found in larger airways.
Overexpression of Th2-cells → inhalation of antigen results in production of cytokines (IL-3, IL-4, IL-5, IL-13) → activation of eosinophils and induction of cellular response (B-cell IgE production) → bronchial submucosal edema and smooth muscle contraction → bronchioles collapse [6][7]
Endobronchial obstruction caused by:
Bronchospasm
Mucosal edema
Hypertrophy of smooth muscle cells
Increased mucus production
Some forms of asthma have specific pathophysiologies:
Allergic asthma: IgE-mediated type 1 hypersensitivity to a specific allergen; characterized by mast cell degranulation and release of histamine after a prior phase of sensitization
Nonallergic asthma
Irritant asthma: irritant enters lung → ↑ release of neutrophils → submucosal edema → airway obstruction
Aspirin-induced asthma: NSAID inhibition of COX-1 → ↓ PGE2 → ↑ leukotrienes and inflammation → submucosal edema → airway obstruction.
I: There is high pitched expiratory wheezing. A combination of clinical findings and objective measurement of pulmonary function (for adults and children ≥ 5 years of age) is needed to confirm the diagnosis and assess the severity of asthma.
Evaluation of pulmonary function
Pulmonary function testing (spirometry)
First-line diagnostic test for confirmation of the diagnosis in patients ≥ 5 years of age.
Shows signs of obstructive lung disease with increased airway resistance → ↓ FEV1, ↓ Tiffeneau index (FEV1/FVC ratio)
Obstruction is reversible with bronchodilators → diagnostic confirmation via post-bronchodilator test
Methacholine challenge test (bronchoprovocation test)
Second-line diagnostic test if pulmonary function testing is nondiagnostic
Evidence of bronchial hyperresponsiveness after inhalation of methacholine
Positive if FEV1 reduced ≥ 20%
Chest x-ray
Usually only indicated in patients with severe asthma to exclude differential diagnoses (e.g., pneumonia, pneumothorax)
Normal in mild cases
Signs of pulmonary hyperinflation in cases of severe asthma
Low, flattened diaphragm
Wide intercostal spaces
Barrel chest.
Laboratory studies and further workup
Pulse oximetry and blood gas analysis (ABG)
Blood gas analysis should be performed if oxygen saturation (SpO2) is < 94%.
Findings on ABG
Initially: ↓ pCO2, ↑ pH, ↓ pO2 leading to type 1 respiratory failure
Ultimately: severe respiratory distress: ↑ pCO2, ↓ pH, and ↓↓ pO2 leading to type 2 respiratory failure.
Patients with acute asthma exacerbations initially have ↓ PCO2 and respiratory alkalosis (↑ pH) due to tachypnea. Rising PCO2 is a sign of respiratory fatigue and impending respiratory failure! ICU admission and intubation should be considered.
In allergic asthma
Antibody testing, total IgE (increased), allergen-specific IgE (increased)
CBC: possibly eosinophilia
Skin allergy tests: skin prick testing (SPT) or intradermal skin testing
In asthma triggered by infection: elevated inflammatory markers
Sputum sample
Curschmann spirals (whorled mucous plug in sputum that is formed by shed bronchial epithelium)
Charcot-Leyden crystals (histopathologic finding in patients with eosinophilic inflammation and/or proliferation)
and/or Creola bodies (aggregate of desquamated epithelial cells).
M: Causal
Avoid triggers (see “Etiology” above).
Allergen immunotherapy in allergic asthma
Early treatment of infections in infection-triggered asthma
If GERD is suspected: proton pump inhibitors.
cute management
For mild symptoms: short-acting beta-2 agonist
For exercise-induced asthma: short-acting beta-2 agonist prior to exercise
For severe asthma exacerbations, see “Treatment” in status asthmaticus.
To remember the meds for asthma exacerbations, think ASTHMA: Albuterol, Steroids, Theophylline (rare), Humidified O2, Magnesium (severe exacerbations), Anticholinergics.
Offer a short-acting beta2 agonist (SABA) as reliever therapy to adults (aged 17 and over) with newly diagnosed asthma. [2017]
- 6.2For adults (aged 17 and over) with asthma who have infrequent, short-lived wheeze and normal lung function, consider treatment with SABA reliever therapy alone. [2017]
- 6.3Offer a low dose of an ICS as the first-line maintenance therapy to adults (aged 17 and over) with:
symptoms at presentation that clearly indicate the need for maintenance therapy (for example, asthma-related symptoms 3 times a week or more, or causing waking at night) or
asthma that is uncontrolled with a SABA alone. [2017]
- 6.4If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS as maintenance therapy, offer a leukotriene receptor antagonist (LTRA) in addition to the ICS and review the response to treatment in 4 to 8 weeks. [2017]
- 6.5If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS and an LTRA as maintenance therapy, offer a long-acting beta2 agonist (LABA) in combination with the ICS, and review LTRA treatment as follows:
discuss with the person whether or not to continue LTRA treatment
take into account the degree of response to LTRA treatment. [2017]
- 6.6If asthma is uncontrolled in adults (aged 17 and over) on a low dose of ICS and a LABA, with or without an LTRA, as maintenance therapy, offer to change the person’s ICS and LABA maintenance therapy to a MART regimen with a low maintenance ICS dose. [2017]
- 6.7If asthma is uncontrolled in adults (aged 17 and over) on a MART regimen with a low maintenance ICS dose, with or without an LTRA, consider increasing the ICS to a moderate maintenance dose (either continuing on a MART regimen or changing to a fixed-dose of an ICS and a LABA, with a SABA as a reliever therapy). [2017]
- 6.8If asthma is uncontrolled in adults (aged 17 and over) on a moderate maintenance ICS dose with a LABA (either as MART or a fixed-dose regimen), with or without an LTRA, consider:
increasing the ICS to a high maintenance dose (this should only be offered as part of a fixed-dose regimen, with a SABA used as a reliever therapy) or
a trial of an additional drug (for example, a long-acting muscarinic receptor antagonist or theophylline) or
seeking advice from a healthcare professional with expertise in asthma.
Long-term management
General principles
Reduce number of asthma attacks → Medical therapy is escalated or de-escalated depending on the patient’s individual needs.
Self-monitoring for patients: peak flow meter to measure peak expiratory flow rate (PEFR)
Patients can avoid exacerbations with frequent PEFR measurements: PEFR decreases before symptoms appear → indicates insufficient medication regimen
Influenza and pneumococcal vaccines are administered in all patients.
Pharmaceutical management
Reliever medications: provide relief of asthma symptoms and are taken as needed when symptoms are present
Controller medications: control underlying inflammation of asthma
Shift in treatment paradigm as of 2019 [13]
Previously: As-needed SABA reliever inhaler was the mainstay of intermittent asthma treatment.
New recommendation: ICS-containing controller inhaler for every adult and adolescent with asthma (no more SABA-only treatment)
Reasoning: ICS addresses the underlying problem of airway inflammation → reduces both frequency of symptoms and risk of severe asthma exacerbations (SABAs only address symptoms)
Note that many resources still list as-needed SABA reliever treatment as the only therapy necessary in intermittent asthma.
Inhaled corticosteroids do not take full effect until they have been used for approx. 1 week!
Monitoring
Routine follow-up every 1–6 months, depending on severity
Purpose of follow-up: assessment of asthma symptom control.
P: Status asthmaticus
Definition: extreme asthma exacerbation that does not respond to initial treatment with bronchodilators
Clinical features
Initially: orthopnea, tachypnea, tachycardia, and cyanosis
Signs of imminent respiratory arrest
Drowsiness/confusion
Paradoxical thoracoabdominal movement
Bradycardia
Absent wheezing
Pulsus paradoxus
Diagnosis
The following diagnostic workups should be done in patients with status asthmaticus attacks:
ABG (i.e., to identify hypercapnia and hypoxemia)
CBC
BMP
Peak expiratory flow measurement
Chest x-ray
ECG (in older patients)
Management
Hospitalization
PEF or FEV1: 50–70% of the predicted value
PEF or FEV1 < 50% of the predicted value → admitted in the ICU
Medications
Short-acting beta-2 agonist (SABA)
Short-acting muscarinic antagonists (SAMA) like ipratropium bromide
Oral corticosteroid
Intravenous magnesium sulfate
Oxygenation and ventilation
Supplemental oxygen and/or helium-oxygen mixture (heliox)
Noninvasive ventilation (NIV)
Bilevel positive airway pressure (BiPAP) provides greater support.
Maintains airways open → decreases airways resistance → reduces auto-PEEP → reduces work of breathing
Use for 1–2 hours in cooperative patients not responding to medical therapy.
Do not delay intubation when it is indicated.
Indications for intubation
Use of accessory muscles
Decreased oxygen saturation
Inability to speak in full sentences
Inadequate response to initial therapy
Normalizing PCO2 or pH (see “Laboratory Studies” under “Diagnostics” above)
Status asthmaticus is a medical emergency, as it can be a life-threatening!
COPD Dr
D: A chronic pulmonary disease characterized by persistent respiratory symptoms and airflow limitation (postbronchodilator FEV1/FVC < 0.70), which is caused by a mixture of small airway obstruction and parenchymal destruction.
COPD was formerly subdivided into chronic bronchitis and emphysema. These terms are still widely used to describe patient findings and found as subclasses of COPD in outdated literature.
Chronic bronchitis: productive cough (cough with expectoration) for at least 3 months each year for 2 consecutive years
Emphysema: permanent dilatation of pulmonary air spaces distal to the terminal bronchioles, caused by the destruction of the alveolar walls and the pulmonary capillaries required for gas exchange.
R- tobacco smoking is a major risk factor for the development of COPD. Suspect COPD in people aged over 35 years occupational or environmental exposure.
copd-deac
D:
Asthma — COPD and asthma can be difficult to distinguish clinically and may co-exist.
Consider asthma if the person has a family history, other atopic disease, or nocturnal or variable symptoms, is a non-smoker, or experienced onset of symptoms at younger than 35 years of age.
For more information, see the CKS topic on Asthma.
Bronchiectasis — clinical features include copious sputum, frequent chest infections, a history of childhood pneumonia, and coarse lung crepitations.
For more information, see the CKS topic on Bronchiectasis.
Heart failure — clinical features include breathlessness when lying flat, a history of ischaemic heart disease, and fine lung crepitations.
For more information, see the CKS topic on Heart failure - chronic.
Lung cancer — consider if the person has a persistent cough, haemoptysis, weight loss, or persistent hoarse voice.
Interstitial lung disease (such as asbestosis, pneumoconiosis, fibrosing alveolitis, or sarcoidosis) — clinical features include a dry cough and fine lung crepitations.
Anaemia — clinical features include fatigue, breathlessness, and palpitations.
Tuberculosis (TB) — clinical features include persistent productive cough, which may be associated with breathlessness and haemoptysis.
Upper airway obstruction (for example tracheal tumour).
E: Sex: 3:2 male/female ratio
The third most common cause of death worldwide
Prevalence: 6%.
A: Exogenous factors
Tobacco use (90% of cases)
Smoking is the major risk factor for COPD, but those who have quit ≥ 10 years ago are not at increased risk.
Passive smoking
Exposure to air pollution or fine dusts
Nonorganic dust: such as industrial bronchitis in coal miners
Organic dust: ↑ incidence of COPD in areas where biomass fuel (e.g., wood, animal dung) is regularly burned indoors
Recurrent pulmonary infections and tuberculosis
Premature birth
Endogenous factors
α1-Antitrypsin deficiency
Antibody deficiency syndrome (e.g., IgA deficiency)
Primary ciliary dyskinesia (e.g., Kartagener syndrome).
C:
Breathlessness — typically persistent, progressive over time, and worse on exertion.
Chronic/recurrent cough.
Regular sputum production.
Frequent lower respiratory tract infections.
Wheeze.
Other symptoms which may be present include:
Weight loss, anorexia and fatigue — common in severe COPD but other causes must be considered.
Waking at night with breathlessness.
Ankle swelling – consider cor pulmonale.
Chest pain – uncommon in COPD, consider other causes.
Haemoptysis – uncommon in COPD, consider other causes.
Reduced exercise tolerance.
Symptoms are minimal or nonspecific until the disease reaches an advanced stage.
Common presenting findings:
Chronic cough with expectoration (expectoration typically occurs in the morning)
Dyspnea and tachypnea
Initial stages: only on exertion
Advanced stages: continuously
Pursed-lip breathing
End-expiratory wheezing, crackles, muffled breath sounds, and/or coarse rhonchi on auscultation
Tachycardia
Cyanosis
Often weight loss and cachexia
In cases of advanced COPD and/or cor pulmonale:
Congested neck veins
Barrel chest
Asynchronous movement of the chest and abdomen during respiration
Use of accessory respiratory muscles due to diaphragmatic dysfunction
Hyperresonant lungs, reduced diaphragmatic excursion, and relative cardiac dullness on percussion
Decreased breath sounds on auscultation: “silent lung” (silent chest on auscultation)
Prolonged expiratory phase
Peripheral edema (most often ankle edema)
Right ventricular hypertrophy with signs of right heart failure
Hepatomegaly
Secondary polycythemia
Confusion
Nail clubbing in the case of certain comorbidities (e.g., bronchiectasis, pulmonary fibrosis, lung cancer)
According to their clinical appearance, patients with COPD are often categorized as either “Pink Puffer” or “Blue Bloater”.
Reduced exercise tolerance.
Examination may be normal. Where present, signs may include:
Cyanosis.
Raised jugular venous pressure and/or peripheral oedema (may indicate cor pulmonale).
Cachexia.
Hyperinflation of the chest.
Use of accessory muscles and/or pursed lip breathing.
Wheeze and/or crackles on auscultation of the chest.
Copd-pimp
P: COPD is characterized by chronic airway inflammation and tissue destruction.
Chronic inflammation: results from significant exposure to noxious stimuli
Caused by increased oxidative stress (most commonly due to cigarette smoke) as well as by increased release of reactive oxygen species by inflammatory cells
Increased number of neutrophils, macrophages, and CD8+ T lymphocytes → release of cytokines → amplification of inflammation and structural changes of lung parenchyma (e.g., growth factor release)
Promotes goblet cell proliferation, mucus hypersecretion, and impaired ciliary function → chronic productive cough
Reid index: The ratio of the width of the mucus-secreting glands to the combined width of the epithelium and cartilage in the bronchial tree. > 0.5 is characteristic of chronic bronchitis.
Overproduction of growth factor → peribronchiolar fibrosis → narrowing of airway → obliteration → emphysema (airflow limitation)
Smooth muscle hyperplasia of the small airways and pulmonary vasculature (mainly due to hypoxic vasoconstriction) → pulmonary hypertension → cor pulmonale
Tissue destruction
Bronchopulmonary inflammation ↑ proteases, and nicotine use (or other noxious stimuli) inactivates protease inhibitors (especially α1-antitrypsin) → imbalance of protease and antiprotease → ↑ elastase activity → loss of elastic tissue and lung parenchyma (via destruction of the alveolar walls), which causes:
Enlargement of airspaces → ↓ elastic recoil and ↑ compliance of the lung → ↓ tethering of small airways → expiratory airway collapse and obstruction → air trapping and hyperinflation → ↓ ventilation (due to air-trapping) and ↑ dead space → ↓ DLCO and ↑ ventilation-perfusion mismatch (Va/Q) → hypoxemia and hypercapnia
↓ Blood volume in pulmonary capillaries → ↑ dead space → ↓ DLCO and ↑ Va/Q → hypoxemia and hypercapnia
Imbalance of oxidants and anti-oxidants and an overabundance of free radicals → contributes to chronic inflammation and inactivation of anti-elastase → exacerbates breakdown of elastic tissue
I: Spirometry and/or body plethysmography
FEV1/FVC < 70% (Tiffeneau-Pinelli index)
Normal or decreased FVC
Decreased FEV1: used to classify COPD according to GOLD (see classification above)
Increased FRC and RV
TLC
Chronic bronchitis: normal
Emphysema: increased
Increased intrathoracic gas volume
DLCO
Chronic bronchitis: normal
Emphysema: decreased
Post-bronchodilator test
Assesses reversibility of bronchoconstriction
Procedure
Spirometry to establish a baseline
Inhalation (e.g., salbutamol)
Perform spirometry again after ∼10–15 min.
Results: FEV1/FVC < 0.7 is diagnostic of COPD (in patients with typical clinical features and exposure to noxious stimuli).
FEV1 > 12% (reversible bronchoconstriction): Asthma is more likely than COPD.
If spirometry is normal, COPD can be excluded.
FEV1 < 12% (irreversible bronchoconstriction): COPD is more likely than asthma.
Blood gas analysis (BGA) and pulse oximetry
Pulse oximetry: assess O2 saturation
BGA: only indicated when O2 is < 92% or if the patient is severely ill (e.g., altered mental status, acute exacerbation)
Hypoxemia and hypercapnia with acute or chronic respiratory acidosis
Decreased pO2: partial respiratory failure
Decreased pO2 and increased pCO2: global respiratory failure
Possibly increased hemoglobin (polycythemia).
Indications: not required for routine diagnosis but often used as an initial modality, mainly to rule out alternative conditions (e.g., pulmonary fibrosis, bronchiectasis)
Chest x-ray
Not sensitive, especially during the early stages of COPD
Can be used to determine the etiology for an acute COPD exacerbation (e.g., pneumonia, congestive heart failure)
Signs of hyperinflated lungs (barrel chest)
Hyperlucency of lung tissue (decreased lung markings)
Increased anteroposterior diameter
Diaphragm pushed down and flattened
Horizontal ribs and widened intercostal spaces
Long narrow heart shadow
Parenchymal bullae or subpleural blebs (pathognomonic of emphysema)
The retrosternal space is increased on lateral view due to emphysematous changes in the lung tissue.
Chest CT
Evaluate possible complications (e.g., pneumothorax, ARDS).
Plan surgery (e.g., lung volume reduction, lung transplantation).
Rule out differential diagnoses (e.g., bronchiectasis, lung cancer).
In most patients with COPD: centriacinar emphysema
In patients with AATD: panacinar emphysema , bronchiectasis, bullae
Other tests
Laboratory studies
Increased serum hematocrit
In patients suspected of AATD (≤ 50 years of age, hepatic symptoms):
α1-Antitrypsin levels
Electrophoresis: decreased alpha-1 peak
Gram stain and sputum culture: in the case of suspected pulmonary bacterial infection (e.g., fever, productive cough, new infiltrate on chest x-ray)
Bronchoscopy: to identify the pathogen in severe and acute exacerbation of COPD with infective etiology, especially if antibiotic treatment fails
Liver biopsy in patients with AATD: PAS-positive, spherical inclusion bodies in periportal hepatocytes.
M:
For less than 1 or 1 exacerbation per year:
Mild symptoms: Any bronchodilator (SABA or LABA)
For severe symptoms: any long aacting bronchodilator (LABA or LAMAA). If severe dyspnea: LABA and LAMA.
For ≥ 2 exacerbation or ≥ 1 exacerbation requiring hospitalization: mild symptoms: LAMA, and severe symptoms:
LAMA or
If highly symptomatic (CAT > 20): LAMA and LABA or
If eosinophil count is ≥ 300/μl: LABA and ICS.
Cessation of tobacco use (single most effective step to slow the decline in lung function)
Vaccinations
Pneumococcal: reduces the incidence of community-acquired pneumonia and invasive pneumococcal diseases
Age 19-64 years: Administer PPSV23.
Age ≥ 65 years
Vaccinated: Administer PPSV23 (should be at least 5 years after the previous PPSV23 dose and at least 1 year after PCV13).
Not vaccinated or unknown vaccination history: Administer PCV13 followed by PPSV23
Immunocompetent patients: Administer PPSV23 after 1 year.
Individuals with immunocompromising conditions, cerebrospinal leaks, or cochlear implants: Administer PPSV23 after 8 weeks.
Influenza (annual): reduces serious illness and death in COPD patients
Pulmonary rehabilitation (indicated in patients with GOLD B, C, and D): physiotherapy with breathing exercises
Pursed lip breathing: A breathing technique in which the patient breathes in through the nose and breathes out slowly through pursed lips. This technique increases airway pressure and prevents bronchial collapse during the last phase of expiration.
Physical activity helps maintain endurance and alleviate dyspnea.
Supportive treatment (e.g., postural drainage)
Vitamin D3 and calcium in cases of deficiency.
Medical treatment in COPD reduces the severity of symptoms, improves overall health status, and lowers the frequency and severity of exacerbation. The first-line treatment of COPD consists of bronchodilators, inhaled corticosteroids, and phosphodiesterase (PDE) type 4 inhibitors.
Bronchodilators: either parasympatholytics (see muscarinic antagonists) or β2-agonists
Long-acting parasympatholytics (long-acting muscarinic antagonists, LAMAs): tiotropium bromide
Long-acting β2-agonists (LABAs): salmeterol, formoterol
Short-acting parasympatholytics (short-acting muscarinic antagonists, SAMAs): ipratropium bromide
Short-acting β2-agonists (SABAs): salbutamol, fenoterol
Inhaled corticosteroids (ICS): budesonide, fluticasone, beclomethasone
PDE type 4 inhibitors: roflumilast
acute exacerbations of copd
An acute exacerbation of chronic obstructive pulmonary disease (COPD) is a sustained worsening of a person’s symptoms from their usual stable state (beyond normal day-to-day variations) which is acute in onset.
Acute exacerbations of COPD can be triggered by a range of factors including respiratory tract infections (most commonly rhinovirus), smoking, and environmental pollutants.
Many exacerbations are not caused by bacterial infections so will not respond to antibiotics.
Commonly reported symptoms include:
Increased breathlessness.
Increased cough.
Increased sputum production and change in sputum colour.
Other reported symptoms may include:
Increased wheeze and chest tightness.
Upper respiratory tract symptoms (for example cold or sore throat).
Reduced exercise tolerance.
Ankle swelling.
Increased fatigue.
Acute confusion.
dxd:
Pneumonia.
For more information, see the CKS topic on Chest infections - adult.
Pulmonary embolism.
For more information, see the CKS topic on Pulmonary embolism.
Pneumothorax.
Acute heart failure.
Pleural effusion.
Cardiac ischaemia or arrhythmia.
For more information, see the CKS topics on Angina and Atrial fibrillation.
Lung cancer.
For more information, see the CKS topic on Lung and pleural cancers - recognition and referral.
Upper airway obstruction.
P: 40–70% of all COPD patients survive the first 5 years after diagnosis
Survival rates vary significantly depending on the severity of the disease. [33]
Measures that improve survival
Cessation of tobacco use
Long-term supplemental O2 therapy is the only treatment that improves mortality. Complications: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
Chronic respiratory failure.
Other complications: Alveolar hypoventilation –> hypoxic pulmonary vasoconstriction –> pulmonary hypertension –> cor pulmonale.
Pulmonary cachexia
Secondary spontaneous pneumothorax
Pulmonary embolus
D: Pulmonary embolism (PE) is the obstruction of one or more pulmonary arteries by solid, liquid, or gaseous masses. In most cases, the embolism is caused by blood thrombi, which arise from the deep vein system in the legs or pelvis (deep vein thrombosis) and embolize to the lungs via the inferior vena cava.
R: Risk factors include immobility, inherited hypercoagulability disorders, pregnancy, and recent surgery. Risk factors: obesity, hypomobility or immobility, malignancy, pregnancy, dehydration , hypercoagulability, use of contraceptives, previous DVT (see risk factors for deep vein thrombosis)
D: Conditions that can cause similar symptoms to pulmonary embolism (PE) include:
Other respiratory conditions, such as:
Pneumothorax.
Pneumonia.
Acute bronchitis.
Acute exacerbation of asthma. For more information, see the CKS topic on Asthma.
Acute exacerbation of chronic obstructive pulmonary disease (COPD). For more information, see the CKS topic on Chronic obstructive pulmonary disease.
Acute exacerbation of chronic lung disease.
Cardiac causes, such as:
Acute coronary syndrome.
Acute congestive heart failure.
Dissecting or rupturing aortic aneurysm.
Unstable angina. For more information, see the CKS topic on Angina.
Myocardial infarction. For more information, see the CKS topic on MI - secondary prevention.
Pericarditis.
Musculoskeletal chest pain. Note that chest pain with chest wall palpation occurs in up to 20% of people with confirmed PE.
Gastro-oesophageal reflux disease. For more information, see the CKS topic on Dyspepsia - proven GORD.
Any cause for collapse, such as:
Vasovagal syncope.
Orthostatic (postural) hypotension.
Cardiac arrhythmias. For more information, see the CKS topic on Atrial fibrillation.
Seizures. For more information, see the CKS topic on Epilepsy.
Cerebrovascular disorders. For more information, see the CKS topic on Stroke and TIA.
Panic disorder. For more information, see the CKS topic on Generalized anxiety disorder.
Post-surgery atelectasis
Anxiety disorders
E: Accounts for ∼ 100,000 deaths in the US per year.
Incidence rises with age.
Sex: ♂ > ♀
A: Deep vein thrombosis (most common cause)
Risk factors: obesity, hypomobility or immobility, malignancy, pregnancy, dehydration , hypercoagulability, use of contraceptives, previous DVT (see risk factors for deep vein thrombosis)
Fat embolism during major surgical interventions (e.g., endoprosthesis replacement, osteosynthesis)
Others: air embolism, amniotic fluid embolism, tissue embolism, cement embolism, bacterial embolism, tumor embolism.
C: clinical presentation is variable and, depending on the extent of vessel obstruction, can range from asymptomatic to cardiogenic shock. Symptoms are often nonspecific, including chest pain, coughing, dyspnea, and tachycardia.
Acute onset of symptoms, often triggered by a specific event (e.g., on rising in the morning, sudden physical strain/exercise)
Dyspnea and tachypnea (> 50% of cases)
Sudden chest pain (∼ 50% of cases), worse with inspiration
Cough and hemoptysis
Possibly decreased breath sounds, dullness on percussion, split-second heart sound audible in some cases
Tachycardia (∼ 25% of cases), hypotension
Jugular venous distension
Low-grade fever
Syncope and shock with circulatory collapse in massive PE (e.g., due to a saddle thrombus)
Symptoms of DVT: unilaterally painful leg swelling.
P: Mechanism: thrombus formation (see Virchow’s triad) → deep vein thrombosis in the legs or pelvis (most commonly iliac vein) → embolization to pulmonary arteries via inferior vena cava → partial or complete obstruction of pulmonary arteries
Pathophysiologic response of the lung to arterial obstruction
Infarction and inflammation of the lungs and pleura
Causes pleuritic chest pain and hemoptysis
Leads to surfactant dysfunction → atelectasis → ↓ PaO2
Triggers respiratory drive → hyperventilation and tachypnea → respiratory alkalosis with hypocapnia (↓ PaCO2)
Impaired gas exchange
Mechanical vessel obstruction → ventilation-perfusion mismatch → arterial hypoxemia (↓ PaO2) and elevated A-a gradient (see “Diagnostics” below)
Cardiac compromise
Elevated pulmonary artery pressure (PAP) due to blockage → right ventricular pressure overload → forward failure with decreased cardiac output → hypotension and tachycardia
Pathophysiology of pulmonary embolism
I: Haemodynamic stability, pre-test probability, D-dimer levels, Arterial blood gas (ABG), CT-pulmonary angiography, Ventilation/perfusion scintigraphy (V/Q scan). echocardiograohy, chest x-ray, pulmonary angiography, ecg. Assess the pretest probability of PE with wells score. The diagnosis of PE is based primarily on the clinical findings and is confirmed by the detection of an embolism in CT pulmonary angiography (CTPA). Arterial blood gas analysis typically shows evidence of respiratory alkalosis with low partial oxygen pressure, low partial carbon dioxide pressure, and elevated pH. Another commonly performed test is the measurement of D-dimer levels, which can rule out PE if negative. Anticoagulation with heparin is initiated to prevent further thromboembolisms as well as to promote the gradual dissolution of the embolism and the underlying thrombosis. In massive PE with shock, the thrombus is resolved with thrombolytic agents or thrombectomy.
Suspect pulmonary embolism (PE) in a person with dyspnoea, tachypnoea, pleuritic chest pain, and/or features of deep vein thrombosis (DVT), including leg pain and swelling (usually unilateral), lower abdominal pain, redness, increased temperature, and venous distension.
Other symptoms that may be present include:
Retrosternal chest pain (due to right ventricular ischaemia).
Cough and haemoptysis.
In severe cases, dizziness and/or syncope (due to right ventricular failure).
Other signs that may be present include:
Tachycardia (heart rate greater than 100 beats per minute).
Hypoxia.
Pyrexia.
Elevated jugular venous pressure.
Gallop rhythm, a widely split second heart sound, tricuspid regurgitant murmur.
Pleural rub.
Hypotension (systolic blood pressure less than 90 mmHg) and cardiogenic shock (rare signs indicating central PE and/or a severely reduced haemodynamic reserve).
The presence of risk factors, such as pregnancy, previous DVT or PE, active cancer, or recent surgery, makes the diagnosis of PE more likely.
Be aware that PE may be completely asymptomatic and be discovered incidentally when assessing for another condition.
If PE is suspected:
Carry out an assessment of their general medical history, a physical examination, and, where necessary, investigations (such as a chest X-ray or electrocardiogram [ECG]) to:
Exclude other causes of symptoms, including other respiratory conditions (such as pneumothorax and pneumonia) and cardiac causes (such as acute coronary syndrome and acute congestive heart failure).
Assess for risk factors (such as pregnancy and immobilization).
Do not delay management for results of a chest X-ray or ECG.
Abnormalities on chest X-ray or ECG are not specific for PE, but might be useful in the differential diagnosis.
Chest X-ray features that may be present include atelectasis, pleural effusion, or elevation of a hemidiaphragm.
ECG signs that may be present include sinus tachycardia, non-specific ST-segment and T-wave abnormalities, right axis deviation.
M:
Stabilize the patient and provide supportive care.
Pulseless patient with suspected PE: Start ACLS and consider administration of thrombolytics (e.g., tPA). [32][33].
Assess bleeding risk (see risk factors for bleeding in patients with VTE).
Consider empiric parenteral anticoagulation while awaiting a definitive diagnosis.
Risk stratify the patient based on prognostic models (see risk stratification of pulmonary embolism).
Consult pulmonary embolism response team (PERT), if available. [34]
Initiate therapy based on risk stratification and bleeding risk.
Massive PE: thrombolytic therapy or thrombectomy.
Submassive and nonmassive PE: anticoagulation or IVC filter
Hemodynamic support: in patients with hypotension [35]
IV fluids
Gentle bolus (e.g., normal saline ≤ 500 mL)
Avoid volume overload, which may be harmful in cases of right ventricular strain
Consider vasopressors (norepinephrine is most commonly used) if there is no improvement following fluid administration.
Respiratory support
Oxygen supplementation in patients with SpO2 < 90% [35]
For patients with respiratory failure: airway management and/or mechanical ventilation
Analgesics: for patients with pain
See pain management.
Avoid NSAIDs if patient receiving anticoagulation or thrombolytics
Consider one of the following:
Morphine
Oxycodone
P:
High risk of recurrence: without anticoagulant treatment ∼ 10% in the first year, ∼ 5% per year after
Right ventricular failure
Sudden cardiac death due to pulseless electrical activity
Atelectasis (∼ 20% of cases)
Pleural effusion
Pulmonary infarction (∼ 10% of cases)
Embolisms of smaller segmental arteries can lead to wedge-shaped hemorrhagic pulmonary infarctions
Right ventricular failure, increased bronchial venous pressure, and preexisting pulmonary diseases increase the risk.
Pneumonia from pulmonary infarction: peripheral infiltration on chest X-ray (typically wedge-shaped = Hampton’s hump)
Pneumothorax DR DEAC PIMP
D: Pneumothorax develops when air enters the pleural space as the result of disease or injury. This leads to a loss of negative pressure between the two pleural membranes, which can result in the partial or complete collapse of the lung. Pneumothorax is classified as spontaneous or traumatic. Spontaneous pneumothorax can be further classified as primary (i.e., no underlying lung disease) or secondary (i.e., due to underlying lung disease). Any type of pneumothorax can progress to tension pneumothorax, which is a life-threatening variant of pneumothorax.
A collection of air within the pleural space between the lung (visceral pleura) and the chest wall (parietal pleura) that can lead to partial or complete pulmonary collapse [2]
May be classified as:
Spontaneous pneumothorax
Primary spontaneous pneumothorax: occurs in patients without clinically apparent underlying lung disease
Secondary spontaneous pneumothorax: occurs as a complication of underlying lung disease
Recurrent pneumothorax: a second episode of spontaneous pneumothorax, either ipsilateral or contralateral
Traumatic pneumothorax: a type of pneumothorax caused by a trauma (e.g., penetrating injury, iatrogenic trauma)
Tension pneumothorax: a life-threatening variant of pneumothorax characterized by progressively increasing pressure within the chest and cardiorespiratory compromise.
R: risk factors of primary pneumothorax: Risk factors
Family history
Male gender
Young age
Asthenic body habitus (slim, tall stature) (e.g., in Marfan syndrome)
Smoking (90% of cases): up to 20-fold increase in risk (risk increases with the cumulative number of cigarettes smoked)
Homocystinuria
D:
could be acute chest pain differentials.
pneumonia, acute asthma exacerbation, bronchitis, pulmonary embolism, aortic dissection, costochondritis, acute coronary syndrome, anxiety or panic attack, diaphragmatic injuries, GERD, esophageal spasm, Mallory-Weiss tear, Boerhaave’s syndrome,
E: Primary spontaneous pneumothorax Sex: ♂ > ♀ (approx. 6:1) Peak incidence: 20–30 years Secondary spontaneous pneumothorax Sex: ♂ > ♀ (approx. 3:1) Peak incidence: 60–65 years
A: Primary: (idiopathic or simple pneumothorax)
Caused by ruptured subpleural apical blebs
Risk factors
Family history
Male gender
Young age
Asthenic body habitus (slim, tall stature) (e.g., in Marfan syndrome)
Smoking (90% of cases): up to 20-fold increase in risk (risk increases with the cumulative number of cigarettes smoked)
Homocystinuria
Secondary (pneumothorax as a complication of underlying lung disease)
COPD (smoking) → rupture of bullae in emphysema
Pulmonary tuberculosis
Cystic fibrosis → bronchiectasis with obstructive emphysema and bleb or cyst rupture
Pneumocystis pneumonia → alveolitis, rupture of a cavity
Catamenial pneumothorax (thoracic endometriosis): extremely rare.
Traumatic pneumothorax: Blunt trauma (e.g., motor vehicle accident in which the thorax hits the steering wheel or rib fracture occurs)
Penetrating injury (e.g., gunshot, stab wound)
Iatrogenic pneumothorax: mechanical ventilation with high PEEP (barotrauma), thoracocentesis, central venous catheter placement, bronchoscopy, lung biopsy.
C:
Patients range from being asymptomatic to having features of hemodynamic compromise. [4]
Sudden, severe, and/or stabbing, ipsilateral pleuritic chest pain and dyspnea
Reduced or absent breath sounds, hyperresonant percussion, decreased fremitus on the ipsilateral side
Subcutaneous emphysema
Addition findings in tension pneumothorax [5]
Severe acute respiratory distress: cyanosis, restlessness, diaphoresis
Reduced chest expansion on the ipsilateral side
Distended neck veins and hemodynamic instability (tachycardia, hypotension, pulsus paradoxus)
Secondary injuries may be present (e.g., open or closed wounds).
Signs of tension pneumothorax in ventilated patients [5]
Tachycardia, hypotension
Rapid decrease in SpO2
Reduced air flow
Increased ventilation pressure
Skin emphysema
Patients with pneumothorax usually present with sudden-onset dyspnea, ipsilateral chest pain, diminished breath sounds, and hyper-resonant percussion on the affected side. Tension pneumothorax further manifests with distended neck veins, tracheal deviation, and hemodynamic instability. There should be a high index of suspicion for both conditions on clinical evaluation. Unstable patients with tension pneumothorax require immediate needle decompression. Chest x-ray may be used to confirm the diagnosis in stable patients. Small pneumothoraces may resorb spontaneously, but larger defects usually require placement of a chest tube.
P: Increased intrapleural pressure → alveolar collapse → decreased V/Q ratio and increased right-to-left shunting
Spontaneous pneumothorax: rupture of blebs and bullae → air moves into pleural space with increasing positive pressure → ipsilateral lung is compressed and collapses
Traumatic pneumothorax
Closed pneumothorax: air enters through a hole in the lung (e.g., following blunt trauma)
Open pneumothorax: air enters through a lesion in the chest wall (e.g., following penetrating trauma)
Air enters the pleural space on inspiration and leaks to the exterior on expiration
Air shifts between the lungs
Tension pneumothorax: disrupted visceral pleura, parietal pleura, or tracheobronchial tree → air enters the pleural space on inspiration but cannot exit → progressive accumulation of air in the pleural space and increasing positive pressure within the chest → collapse of ipsilateral lung and compression of contralateral lung, trachea, heart, and superior vena cava → impaired respiratory function, reduced venous return to the heart and reduced cardiac output → hypoxia and hemodynamic instability
Open and closed pneumothoraxTension pneumothorax.
I: Chest x-ray, ultrasound, CT can provide information about the underlying cause (e.g., bullae in spontaneous pneumothorax). Tension pneumothorax is primarily a clinical diagnosis and prolonged diagnostic studies should be avoided in favor of initiating immediate treatment.
M: respiratory support
Upright positioning
Provide supplemental high-flow oxygen as needed (target SpO2 ≥ 96%) [4]
If a patient requires mechanical ventilation, emergency chest tube placement is indicated.
Positive pressure ventilation can turn a simple pneumothorax into a life-threatening tension pneumothorax.
Decompression of a pneumothorax can sometimes rapidly improve dyspnea, making mechanical ventilation unnecessary.
See also airway management and oxygen therapy.
Needle thoracostomy
Indication: tension pneumothorax
Procedure:
Immediate insertion of a large-bore needle into the second intercostal space along the midclavicular line
Typically followed by the insertion of a chest tube
Chest tube placement [19]
Indications: see above
Procedure
Most commonly in the 4th–5th intercostal space (nipple line), between the anterior and median axillary line (safe triangle )
Rarely: second intercostal space, midclavicular line (Monaldi drain)
The intercostal space is very narrow at this site and the pectoralis muscle must be penetrated. [19]
Primarily used for emergency chest decompression
Connect tubing to water seal or suctioning [4]
Always check CXR after the procedure is complete.
P: Complete pulmonary collapse → respiratory failure
Tension pneumothorax → cardiac failure
Mediastinal flutter in case of open pneumothorax → hemodynamic shock
Hemothorax in cases of trauma
Pneumomediastinum
Pneumoperitoneum
Recurrence
Post-surgical/-procedural complications
Persistent fistula with continuous air leak
Injury to intercostal nerves and vessels
Infection
Pneumonia DR DEAC PIMP
D:Pneumonia is a respiratory infection characterized by inflammation of the alveolar space and/or the interstitial tissue of the lungs. In industrialized nations, it is the leading infectious cause of death. Pneumonia is most commonly transmitted via aspiration of airborne pathogens (primarily bacteria, but also viruses and fungi) but may also result from the aspiration of stomach contents. The most likely causal pathogens can be narrowed down based on patient age, immune status, and where the infection was acquired (community-acquired or hospital-acquired).
R: Risk factors
Old age and immobility of any cause
Chronic diseases
Pre-existing cardiopulmonary conditions (e.g., bronchial asthma, COPD, heart failure)
Acquired or congenital abnormalities of the airways (e.g., bronchiectasis, space-occupying lesions, cystic fibrosis)
Immunosuppression (e.g., HIV infection, diabetes mellitus, cytostatic therapy, alcoholism, immunosuppressive therapy, malnutrition)
Smoking
Impaired airway protection → aspiration
Alteration in consciousness (e.g., stroke, seizure, anesthesia, drugs, alcohol)
Dysphagia
Environmental factors
Crowded living conditions (e.g., prisons, homeless shelters)
Toxins (e.g., solvents, gasoline)
Cryptogenic organizing pneumonia
Specific medications (e.g., amiodarone, bleomycin)
Chronic inflammatory disorders (e.g., rheumatoid arthritis).
D: Several diseases can present with similar signs and symptoms to pneumonia, such as: chronic obstructive pulmonary disease, asthma, pulmonary edema, bronchiectasis, lung cancer, and pulmonary emboli.
E: The annual incidence of Community Acquired Pneumonia is 500–1100 per 100,000 of the adult (aged 18 years
and over) population. CAP is diagnosed in 5–12% of adults who present to GPs with
NICE clinical guideline: Pneumonia scope (September 2012) 2 of 8
symptoms of lower respiratory tract infection, and 22–42% of these patients are
admitted to hospital. The incidence of CAP and of hospital admissions for CAP
varies with patient age and is higher in older people. Between 1.2 and 10% of adults
admitted to hospital with CAP are managed in an intensive care unit. In the UK, mortality in patients with CAP that is managed in the community is less
than 1%. In patients admitted to hospital with CAP mortality is between 5.7 and
14%, and in those admitted to an intensive care unit mortality is over 30%. More
than half (60%) of pneumonia deaths occur in people older than 84.
A: Community acquired pneumonia: Strep. pneumoniae (most commmon). Haemophilus influenzae, moraxella catarrhalis, klebsiella pneumoniae, staphyloccus aureus. Viruses that can cause it: RSV, Influenza virus, CMV, Adenovirus.
C: Typical pneumonia is characterized by a sudden onset of symptoms caused by lobar infiltration.
Severe malaise
High fever and chills
Productive cough with purulent sputum (yellow-greenish)
Crackles and decreased bronchial breath sounds on auscultation
Enhanced bronchophony, egophony, and tactile fremitus
Dullness on percussion
Tachypnea and dyspnea (nasal flaring, thoracic retractions)
Pleuritic chest pain when breathing, often accompanying pleural effusion
Pain that radiates to the abdomen and epigastric region (particularly in children).
Atypical pneumonia typically has an indolent course (slow onset) and commonly manifests with extrapulmonary symptoms.
Nonproductive, dry cough
Dyspnea
Auscultation often unremarkable
Common extrapulmonary features include fatigue, headaches, sore throat, myalgias, and malaise.
P:
Routes of infection
Most common: microaspiration (droplet infection) of airborne pathogens or oropharyngeal secretions
Aspiration of gastric acid (aspiration pneumonitis) , food, or liquids
Hematogenous dissemination (rare)
Pathogenesis
Failure of protective pulmonary mechanisms (cough reflex, mucociliary clearance , alveolar macrophages )
Pathogen infiltrates pulmonary parenchyma → interstitial and alveolar inflammation
Impaired alveolar ventilation → ventilation/perfusion (V/Q) mismatch with intrapulmonary shunting (right to left)
Hypoxia due to increased alveolar-arterial oxygen gradient
Hypoxia is worsened when the affected lung is in the dependent position, as perfusion to the dependent lung is better compared to the nondependent lung.
In the case of a large unilateral pulmonary abscess, it may be helpful to position the patient so that the affected lung is in the dependent position in order to prevent pus from filling the unaffected lung.
I: Pneumonia is a clinical diagnosis based on history, physical examination, laboratory findings, and CXR findings. Consider microbiological studies and advanced diagnostics based on patient history, comorbidities, severity, and entity of pneumonia.
Lab studies include:
-complete blood count.
-Inflammatory markers (Increased CRP, ESR, Leukocytosis. ABG, LFTs (liver function tests) BMP (basic metabolic panel).Imaging: chest x-ray: posteroanterior and lateral. Findings may include: lobar pneumonia (opacity in one or more pulmonary lobes). Bronchopneumonia (poorly defined patchy infiltrates scattered throughout the lungs, atypical or interstitiaal pneumonia, diffuse reticular opacity, absent (or minimal) consolidation). Can also do a chest CT without contrast if inconclusive chest x-ray, recurrent pneumonia, poor response to treatment. Can do a bronchoscopy, diagnostic thoracentesis.
Oxygen saturation – <92% is worrying
Usually an x-ray is performed after clinical suspicion to confirm the diagnosis. The x-ray may show:
Evidence of infiltrate in the form of consolidation on the x-ray – can also show the spread of any infection by distribution of the infiltrate
Changes may not appear on x-ray for up to 48 hours after symptoms, however, after effective treatmnet, consolidation may still be seen on x-ray for up to 6 weeks
Persistent x-ray changes may suggest underlying carcinoma with secondary pneumonia
X-ray should be repeated at least weekly as an inpatient, and then at 6 weeks follow-up. Any signs still present indicate the need for a further x-ray.
Blood cultures may be taken to asses for bacteraemia.
It is not routine practice to attempt to identify the causatory organism in community acquired infection.
FBC
↑WCC
↑ESR (>100mm/h) and ↑CRP
Possible anaemia (sign of abscess)
Blood cultures – in ill patients to check for septicaemia
Urine – in severe cases of pneumonia, where legionella is suspected, urine testing for legionella antigen may be indicated
Pleural fluid aspiration – to asses for organisms. Transthoracic aspiration may be performed (often with CT guidance) to identify lesions (e.g. empyema, abscess) and to gain samples.
The CURB-65 score – is a scale used to assess the severity of community-acquired pneumonia. It predicts the risk of mortality (CURB score 0 = <1% risk, CURB score 5= 60% risk). Each factor of the score is worth 1 point.
C – Confusion – use the abbreviated mental test (score ≤8)
U – Urea – >7mmol/L
Respiratory rate – ≥30/min
Blood Pressure <90 systolic, or <60 diastolic
65 – age >65 years
A score ≥3 is severe pneumonia. ≥2 requires hospitalisation.
M: The pneumonia severity index (PSI) and the CURB-65 score are tools that can help to determine whether to admit a patient.
CURB-65 score [19]
Confusion (disorientation, impaired consciousness)
Serum Urea > 7 mmol/L (20 mg/dL)
Respiratory rate ≥ 30/min
Blood pressure: systolic BP ≤ 90 mm Hg or diastolic BP ≤ 60 mm Hg
Age ≥ 65 years
Interpretation
Each finding is assigned 1 point.
CURB-65 score 0 or 1: The patient may be treated as an outpatient.
CURB-65 score ≥ 2: Hospitalization is indicated.
CURB-65 score ≥ 3: Consider ICU level of care.
CRB-65 score (if serum urea is not known or unavailable)
CRB-65 score of 0: The patient may be treated as an outpatient.
CRB-65 score of ≥ 1: Hospitalization is recommended.
Empiric antibiotic therapy for community-acquired pneumonia in an outpatient setting
Previously healthy patients without comorbidities or risk factors for resistant pathogens:
Monotherapy with one of the following:
Amoxicillin
Doxycycline
A macrolide (only in areas with a pneumococcal macrolide resistance < 25%)
Azithromycin
Clarithromycin.
Patients with comorbidities or risk factors for resistant pathogens: Combination therapy
An antipneumococcal β-lactam:
Amoxicillin-clavulanate
Cefuroxime
Cefpodoxime
PLUS one of the following:
A macrolide
Azithromycin
Clarithromycin
Doxycycline
Monotherapy: with a respiratory fluoroquinolone
Gemifloxacin
Moxifloxacin
Levofloxacin.
Duration of treatment
5 days of therapy is usually sufficient for CAP that is treated in the outpatient setting.
Any patient being treated in a primary care setting should be re-examined after 48–72 hours to evaluate the efficacy of the prescribed antibiotic.
Additional considerations: Knowing local resistance patterns of S. pneumoniae to macrolides is critical when deciding on an empiric antibiotic regimen.
P: Mortality increases with age. The mortality risk can be evaluated with the CURB-65 score. Score 0: ∼ 1% Score 1–2: ∼ 10% Score 3: ∼ 14% Score 4: ∼ 40% HAP is associated with a mortality rate of > 20%.
Complications: Parapneumonic pleuritis
Fibrinous pleuritis: inflammation → increased vessel permeability → fibrin-rich exudate deposited on the serosal surface of the pleura
May manifest with pleuritic chest pain and friction rub
Analgesics can be used for relief of symptoms.
Parapneumonic pleural effusion (common)
Pleural empyema
Sepsis
Respiratory failure, ARDS
Lung abscess
Pattern of involvement in pneumonia
Lobar pneumonia
Classic (typical) pneumonia of an entire lobe; primarily caused by pneumococci
Characterized by inflammatory intra-alveolar exudate, resulting in consolidation
Can involve the entire lobe or the whole lung.
Bronchopneumonia: mostly commonly a descending infection that affects the bronchioles and adjacent alveoli; usually involves the lower lobes or right middle lobe; manifests as typical pneumonia [8]
Primarily caused by pneumococci and/or other streptococci
Necrotizing bronchopneumonia and pneumatocele are caused by Staphylococcus aureus and are often preceded by an influenza infection.
Characterized by acute inflammatory infiltrates that fill the bronchioles and the adjacent alveoli (patchy distribution)
Usually affects ≥ 1 lobe
Interstitial pneumonia: interstitial inflammation, typically caused by mycoplasma and viral infections; manifests as atypical pneumonia
Characterized by a diffuse patchy inflammation that mainly involves the alveolar interstitial cells
Bilateral multifocal opacities are classically found on chest x-ray.
Often has an indolent course (walking pneumonia)
Miliary pneumonia: multiple small infiltrations caused by hematogenous dissemination (e.g., of tuberculosis)
Cryptogenic organizing pneumonia: characterized by inflammation of the bronchioles and surrounding structures.
Deep vein thrombosis DR DEAC PIMP
D: Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein of the legs, thigh, or pelvis. Thrombosis is most often seen in individuals with a history of immobilization, obesity, malignancy, or hereditary thrombophilia. Vascular endothelial damage, venous stasis, and hypercoagulability, collectively referred to as the Virchow triad, are the main factors contributing to the development of DVT.
R: History of DVT or PE (30x increased risk) [1]
Immobilization: e.g., post-surgery, long-distance flights, trauma (20x increased risk)
Age > 60 years
Malignancy
Hereditary thrombophilia (especially factor V Leiden)
Pregnancy, estrogen use (oral contraceptives)
Obesity
Smoking
IV drug use
Nephrotic syndrome
Insufficient thrombosis prophylaxis, noncompliance with prophylaxis.
To remember the risk factors of deep vein thrombosis, think “THROMBOSIS”: Travel, Hypercoagulable/HRT, Recreational drugs, Old (> 60), Malignancy, Blood disorders, Obesity/Obstetrics, Surgery/Smoking, Immobilization, Sickness (CHF/MI, IBD, nephrotic syndrome, vasculitis)!
D: Superficial thrombophlebitis
Definition: Inflammation and thrombosis of a superficial vein, most commonly in the leg. It may co-exist with DVT, and it rarely causes PE.
Risk factors: same as for DVT (see risk factors for deep vein thrombosis above), but also
Varicose veins
Venous cannulation, IV drug administration
Behçet disease
Thromboangiitis obliterans [19]
Variants
Thrombophlebitis migrans (Trousseau syndrome)
Superficial thrombophlebitis of the breast (Mondor disease)
Clinical features: pain, tenderness, induration, and erythema overlying a superficial vein, often with a palpable cord (the thrombosed vein)
Diagnostics
Typically a clinical diagnosis
Duplex ultrasound
Indicated if the clinical diagnosis is not clear
Findings: A thickened, edematous, noncompressible vessel with or without an intraluminal thrombus
Tests to diagnose the underlying cause.
E:
Venous thrombosis, comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), occurs with an incidence of approximately 1 per 1000 annually in adult populations (1). Rates are slightly higher in men than women.
A: The blood clots of deep vein thrombosis can be caused by anything that prevents your blood from circulating or clotting normally, such as injury to a vein, surgery, certain medications and limited movement. (i) ‘hypercoagulability’, either systemic or local; 30 (ii) ‘stasis’ of the venous blood; and (iii) injury to the vein wall intima, specifically the endothelium. Vascular endothelial damage, venous stasis, and hypercoagulability, collectively referred to as the Virchow triad.
C: May be asymptomatic
Localized unilateral symptoms
Typically affects deep veins of the legs, thighs, or pelvis
More common in the left lower extremity
May-Thurner syndrome: compression of the left iliac vein between the right iliac artery and a lumbar vertebral spur (occurs in > 20% of adults) [6][7]
Swelling, feeling of tightness or heaviness
Warmth, erythema, and possibly livid discoloration
Progressive tenderness, dull pain
Homan sign: calf pain on dorsal flexion of the foot
Meyer sign: Compression of the calf causes pain.
Payr sign: pain when pressure is applied over the medial part of the sole of the foot
Distention of superficial veins
Distal pulses are normal
General symptoms: fever [8]
Possible signs of pulmonary embolism: dyspnea, chest pain, dizziness, weakness.
P: The Virchow triad
The Virchow triad refers to the three main pathophysiological components of thrombus formation.
Hypercoagulability: increased platelet adhesion, thrombophilia (e.g., Factor V Leiden mutation), use of oral contraceptives, pregnancy
Endothelial damage: inflammatory or traumatic vessel injuries can lead to activation of clotting factors through contact with exposed subendothelial collagen
Venous stasis: varicosis, external pressure on the extremity, immobilization (e.g., hospitalization, bed rest, long flights or bus rides), local application of heat
To remember the three pathophysiological components of thrombus formation, think: “HE’S Virchow”: H-Hypercoaguability, E-Endothelial damage, S-Stasis.
I: Wells score. Compression ultrasonography and D-dimer levels are the main diagnostic tests.
Wells score: Interpretation
2 risk group
< 2: DVT unlikely (low risk)
≥ 2: DVT likely (high risk)
OR 3 risk group
0: low risk
1–2: moderate risk of DVT
≥ 3: high risk of DVT.
Compression ultrasonography with Doppler (test of choice)
Description
A combination of ultrasonography (to visualize the vein) and Doppler (to assess blood flow abnormalities) in which the examiner applies gentle pressure to normally compressible veins using an ultrasound probe
High sensitivity and specificity in the popliteal and femoral veins, but very operator dependent
Indications: clinical suspicion of a DVT or pulmonary embolism
Findings: noncompressibility of the obstructed vein, visible hyperechoic mass, absent or abnormal flow in Doppler imaging
D-dimer testing
High sensitivity (∼ 95%), low specificity (∼ 50%)
Useful for ruling out DVT (normal D-dimer levels rule out DVT)
Elevated D-dimers alone are not proof of DVT.
Further diagnostic tests include: venography, CT scan, thrombophilia screening, general tumour screening.
M: Anticoagulation: Acute therapy, heparin bolus plus constant heparin infusion for 4-5 days.
Secondary prophylaxis: -Warfarin with target therapeutic INR of 2.0-3.0.
-OR direct oral factor Xa inhibitor (i.e., rivaroxaban, apixaban). Duration of treatment: at least 3 months.
Thrombolysis, thrombectomy, IVC filter, compression therapy with bandages or compression stockings. Early mobilization as early as tolerated, minimize bedrest.
P: Prognosis is generally good with prompt, adequate treatment.
Complications: Pulmonary embolism
Postthrombotic syndrome (chronic venous insufficiency)
Pulmonary tuberculosis Dr Deac PIMP
D: Tuberculosis (TB) is a common infectious cause of morbidity and mortality worldwide that is caused by Mycobacterium tuberculosis and typically affects the lungs. Primary infection, which is transmitted via airborne droplets, is often initially asymptomatic. Typically, M. tuberculosis remains dormant as the host’s immune system keeps it in check (latent tuberculosis). However, if the immune system becomes compromised, reactivation disease may occur.
R: Immunosuppression (TB is considered to be the most common cause of mortality in patients with HIV globally)
Drug abuse
Alcoholism
Malnutrition
Diabetes mellitus
Pre-existing damage to the lungs (e.g., silicosis, COPD)
Poverty
Residents and employees of congregate settings (e.g., prisons, hospitals, homeless shelters)
Treatment with TNF-α inhibitors
D: brucellosis, bronchogenic carcinoma, Hodgkin lymphoma, bacterial pneumonia, sarcoidosis, mycoplasmal pneumonia.
Atypical pneumonia
Lung cancer.
E: Sex: ♂ > ♀ (2:1)
United States
The incidence of TB infection in the US has been slowly declining.
Foreign-born individuals (especially Asians and Hispanics) account for two-thirds of new TB cases.
Globally
A leading infectious cause of death worldwide
Despite ∼ 1 in 3 individuals being infected with TB worldwide, the overall incidence and prevalence have been declining.
Countries with the highest incidence of TB: India, Indonesia, China, Nigeria, Pakistan, and South Africa
The incidence of multidrug-resistant tuberculosis is steadily rising
A: Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis-rod shaped bacteria). TB is contagious. This means the bacteria is easily spread from an infected person to someone else. You can get TB by breathing in air droplets from a cough or sneeze of an infected person
C: Latent infection
Asymptomatic
The patient is not contagious.
Active infection (either primary or reactivated)
Constitutional symptoms: fever, weight loss, night sweats, fatigue, lymphadenopathy
Pulmonary symptoms: dyspnea, productive cough (possibly hemoptysis) lasting > 3 weeks
The patient is contagious
80% pulmonary tuberculosis
20% extrapulmonary tuberculosis
P: Alveolar macrophages (CD14+) phagocytose the TB bacteria but cannot eliminate them.
Cord factor (trehalose-6,6’-dimycolate): a glycolipid in the cell wall of M. tuberculosis that inhibits fusion of phagosome and lysosome, thereby preventing lysis of phagocytosed mycobacteria
By hiding inside the macrophages, TB bacteria do not provoke a humoral immune response (antibody production by B lymphocytes) in the host → therefore, antibody detection tests play no role in the diagnosis of TB.The mycobacteria replicate safely within the macrophages
Phagocytosed M. tuberculosis can only be destroyed by activated T lymphocytes.
The infection is usually contained in the lung by formation of caseating granulomas (see “Pathology” below) that limit damage to the lungs and bacterial dissemination.
Granuloma formation is caused by a delayed T cell-mediated reaction (i.e., type IV hypersensitivity reaction) that leads to the activation of alveolar macrophages (i.e., epithelioid cells) and their fusion into multinucleated giant cells.
The bacteria may remain dormant in the granulomas for many years without any active clinical disease manifesting (latent TB).
Immunosuppression (compromised T cell function) → dormant bacteria become active, replicate in the macrophages and spread into the lungs and other organs (active TB).
IFN-γ deficiency: impaired phagocytosis and impaired granuloma formation → disseminated TB.
Patients with active disease classically present with fever, weight loss, night sweats, and a productive cough (with or without hemoptysis) that does not respond to conventional antibiotic therapy. The infection may spread hematologically to any organ. However, disseminated disease is rare, unless the patient is severely immunocompromised. Patients with possible latent TB infection (LTBI) should be tested using the purified protein derivative (PPD) skin test or γ-interferon release assay (IGRAs) and be treated accordingly. Treatment of LTBI reduces the risk of active infection in up to 90% of cases, and therefore plays a crucial role in active TB prevention. Any suspicion of active TB infection should be followed by imaging and an attempt to identify M. tuberculosis using microscopy, cultures, and/or polymerase chain reaction (PCR).
I: Chest x-ray, sputum sample, culture Test patients at risk for reactivation or new LTBI who would benefit from treatment of LT. Tuberculous granuloma
Activated macrophages and other immune cells surround the site of infection
Caseous necrosis: multiple activated macrophages that form a conglomerate (polynuclear Langhans giant cells).
Calcium deposits visible on x-ray.
M: Isolation: Every patient diagnosed with active TB must be isolated until sputum, gastric juices, and urine are negative!
Therapy monitoring
Monthly sputum samples for microscopy and culture
Monitor drug side effects: renal retention parameters, ophthalmological check-up , ENT, and liver function tests
Active disease
Initiation phase: 2 months of isoniazid + rifampin + pyrazinamide + ethambutol
Continuation phase: 4 months of isoniazid + rifampin
First-line treatment.
“RIPE” is the acronym for four drugs used in first-line treatment: Rifampin, Isoniazid, Pyrazinamide, and Ethambutol.
The treatment of tuberculosis is a lengthy process due to the slow growth of M. tuberculosis, its concealment in macrophages, and the fact that drugs cannot easily penetrate its cell wall. The standard empirical treatment includes combination therapy with rifampin, isoniazid, ethambutol, and pyrazinamide for 2 months, followed by rifampin and isoniazid for an additional 4 months. Despite combination therapy, the incidence of multidrug-resistant tuberculosis is steadily increasing.
Rifampicin can cause red/orange discolouration of secretions like urine and tears. It is a potent inducer of cytochrome P450 enzymes therefore reduces the effect of drugs metabolised by this system. This is important for medications such as the contraceptive pill.
Isoniazid can cause peripheral neuropathy. Pyridoxine (vitamin B6) is usually co-prescribed prophylactically to reduce the risk of peripheral neuropathy.
Pyrazinamide can cause hyperuricaemia (high uric acid levels) resulting in gout.
Ethambutol can cause colour blindness and reduced visual acuity.
Rifampicin, isoniazid and pyrazinamide are all associated with hepatotoxicity
P:
For most people who live in areas where diagnosis and treatment is available, the prognosis of TB is good if they complete the treatment protocols. The recurrence rate of TB is low (0%-14%) and some may be due to reinfection. Drug-resistant tuberculosis is more difficult to treat, and the prognosis is not as good.
While TB is a serious condition that can be fatal if left untreated, deaths are rare if treatment is completed.
Most people do not need to be admitted to hospital during treatment.
Bronchiectasis DR DEAC PIMP
D: Bronchiectasis is an irreversible and abnormal dilation in the bronchial tree that is generally caused by cycles of bronchial inflammation in addition to mucous plugging and progressive airway destruction. Although the widespread use of antibiotics has made bronchiectasis rare, conditions such as cystic fibrosis (CF), severe or protracted pneumonia, immunodeficiency, and COPD continue to cause it. The most important clinical finding is a chronic cough with copious mucopurulent sputum.
Bronchiectasis may be caused by cystic fibrosis (CF), a genetic condition that results in long-lasting lung infections and reduced ability to breathe. CF gets worse over time. For non-CF bronchiectasis, the cause is not always know.
R: cystic fibrosis, primary ciliary dyskinesia, exposure to chemical irritants, connective tissue disease, immunodeficiencies, allergic bronchopulmonary aspergillosis (ABPA), and history of childhood infections such as pneumonia, tuberculosis, measles.
D: asthma exacerbation, viral respiratory infection, or pneumonia, emphysema.
E: From 2008 to 2012 prevalence increased by 20%, with the number of people recorded to be living with bronchiectasis going up by 40,000. Other research published this year suggests bronchiectasis prevalence could be in excess of 300,000..
A: Bronchiectasis requires the combination of two important processes taking place in the bronchi: local infection or inflammation and either inadequate clearance of secretions, airway obstruction, or impaired host defenses.
Pulmonary infections (i.e., bacterial, viral, fungal), especially severe or chronic infections
Disorders of secretion clearance or mucous plugging
Cystic fibrosis (CF)
Primary ciliary dyskinesia (PCD)
Allergic bronchopulmonary aspergillosis (ABPA)
Bronchial narrowing or other forms of obstruction
COPD
Aspiration
Tumors
Immunodeficiency (e.g., common variable immunodeficiency, hypogammaglobulinemia, HIV)
Chronic inflammatory diseases (e.g., rheumatoid arthritis, Sjögren syndrome, Crohn’s disease).
C: Chronic productive cough (lasting months to years) with copious mucopurulent sputum ; the following may be heard on auscultation:
Crackles and rhonchi
Wheezing (due to obstruction from secretions, airway collapsibility, or a concomitant condition)
Bronchophony
Rhinosinusitis
Dyspnea
Hemoptysis: usually mild/self-limiting but severe hemorrhage that requires embolization may occur.
Nonspecific symptoms (i.e., fatigue, weight loss, pallor due to anemia)
Clubbing of nails (uncommon)
Exacerbations of bronchiectasis
Increased production of mucous above baseline
Low-grade fever
Bronchiectasis should be suspected in a patient with chronic cough producing large amounts of sputum!
P:
I: Imaging
Chest x-ray (best initial test)
Inflammation and fibrosis of bronchial walls lead to the appearance of parallel “tram track” lines
Thin-walled cysts (i.e., dilated bronchi forming sacs), possibly with air-fluid levels
Late-stage bronchiectasis: honeycombing
High-resolution computer tomography (HRCT): confirmatory test
Dilated bronchi with thickened walls; possible signet-ring appearance and tram track lines
Cysts, especially at bronchial ends in lower lobes, and honeycombing
Other tests
Sputum culture and smear: to determine infectious etiology (i.e. bacteria, mycobacteria, and fungi)
Blood tests
CBC with differential: may show anemia of chronic disease and ↑ WBCs, ↑ neutrophils
HIV testing, genetic testing for CF, immunoglobulin quantitation to determine other possible etiologies
Pulmonary function tests: findings consistent with obstructive pulmonary disease (i.e. ↓ FEV1/FVC ratio)
Bronchoscopy: to visualize tumors, foreign bodies, or other lesions; may also be used in combination with bronchoalveolar lavage (BAL) to obtain specimens for staining and culture.
M: Bronchiectasis is a permanent anatomical malformation and therefore cannot be cured. However, symptoms and advancement of the disease can be controlled. The treatment of any underlying cause is also very important.
Conservative
Bronchopulmonary hygiene and chest physiotherapy: “cupping and clapping” and postural drainage, hydration, directed cough
Antibiotic therapy of exacerbations
Smoking cessation
Vaccinations (i.e. seasonal influenza vaccine, pneumococcal vaccine)
Bronchodilators, corticosteroids, and nebulized hypertonic saline are not routinely used but may be considered, especially in patients with notable obstructive symptoms.
Invasive procedures
Surgical resection of bronchiectatic lung or lobectomy: indicated in pulmonary hemorrhage, inviability of bronchus, and substantial sputum production in unilateral bronchiectasis
Pulmonary artery embolization: indicated in pulmonary hemorrhage
Lung transplantation should be considered in severe disease.
P: Recurrent bronchopulmonary infections → obstructive ventilation disorder → respiratory failure and cor pulmonale
Pulmonary hemorrhage (massive hemoptysis)
Pleural empyema
Lung abscess.
Cystic fibrosis DR DEAC PIMP
D: Cystic fibrosis (CF) is an autosomal recessive disorder caused by a mutation in the CFTR gene, which encodes for the cystic fibrosis transmembrane conductance regulator protein. The mutation leads to the production of defective chloride channels in cell membranes of the exocrine glands, and symptoms are caused by these glands producing abnormally hyperviscous secretions.
R:
D:
E: Second most common hereditary metabolic disorder in white populations
Most common lethal genetic disorder in white populations
Incidence
Non-Hispanic whites: ∼1/3300
Heterozygote frequency among non-Hispanic whites: 1/25. Children of heterozygous parents have a 25% chance of developing cystic fibrosis!
A: Hereditary autosomal recessive disorder Defective CFTR (cystic fibrosis transmembrane conductance regulator) protein due to mutation in CFTR gene The most common mutation is delta F508 on chromosome 7. Delta F508 (ΔF508 mutation) denotes the absence of the amino acid phenylalanine (F) in position 508 of the protein (present in 70% of non-Hispanic white patients with CF).
C:
GI symptoms: meconium ileus in newborns, failure to thrive, pancreatic diseaase (fatty stools/foul smelling steatorrhea), malabsorption, abdominal distension, CF-related diabetes mellitus, liver and bile duct abnormalities, intestinal obstruction, rectal prolapse.
Resp symptoms: obstructive lung disease, chronic sinusitis, chronic productive cough, airway hyperreactivity eg wheezing, digital clubbing associated with chronic hypoxia. Salty-tasting sweat –> electrolyte wasting, hyperhidrosis, frequent fractures because of osteopenia, kyphoscoliosis.
Urinary: nephrolithiasis, nephrocalcinosis, frequent urinary tract infections, obstructive azoospermia, undescended testicles in men. In women: viscous cervical mucus, menstrual abnormalities, delayed secondary sexual development in both sexes.
Failure to pass meconium (meconium ileus) is often the first clinical sign of cystic fibrosis. Later, the lungs, digestive system, and sweat glands are commonly affected. Bronchial accumulation of hyperviscous mucus and impaired ciliary clearance predispose patients to chronic respiratory infection, pulmonary colonization with multiresistant bacteria, and long-term complications such as emphysema. Impaired secretion of pancreatic and biliary juices leads to digestive problems and chronic organ damage. The sweat test (pilocarpine iontophoresis) is considered the gold standard for detecting elevated levels of chloride in sweat, which is a characteristic sign of cystic fibrosis.
P: The CFTR gene, which is located on the long arm of chromosome 7, encodes the CFTR protein, which is an important component of the ATP-gated chloride channel in cell membranes.
Mutated CFTR gene (ΔF508 mutation) → misfolded protein → defective protein is retained in the rough endoplasmic reticulum (rER) for degradation → ATP-gated chloride channel is absent on the cell surface of epithelial cells throughout the body (e.g., intestinal and respiratory epithelia, sweat glands, exocrine pancreas, exocrine glands of reproductive organs)
In sweat glands: The chloride channel is responsible for transporting Cl- from the lumen into the cell (reabsorption).
Defective ATP-gated chloride channel → inability to reabsorb Cl- from the lumen of the sweat glands → reduced reabsorption of Na+ and H2O → excessive loss of salt and elevated levels of NaCl in sweat
In all other exocrine glands: The chloride channel is responsible for transporting Cl- from the cell into the lumen (secretion).
Defective ATP-gated chloride channel → inability to transport intracellular Cl- across the cell membrane → reduced secretion of Cl- → accumulation of intracellular Cl- → ↑ Na+ reabsorption (via ENaC) → ↑ H2O reabsorption → formation of hyperviscous mucus → accumulation of secretions and blockage of small passages of affected organs → chronic inflammation and remodeling → organ damage (see “Clinical features” below for details)
↑ Na+ reabsorption → transepithelial potential difference between interstitial fluid and the epithelial surface increases (i.e., becomes more negative: e.g., from normal -13 mv to abnormal -25 mv).
I: In most cases, CF is suspected based on clinical features, a positive newborn screen, or a sibling with CF.
Best initial test is the sweat chloride test.
If results are abnormal or borderline, DNA testing for the two CFTR mutations is indicated to confirm the diagnosis.
If only one or no CFTR mutations are identified, an expanded DNA analysis or second sweat test should be performed; a positive result on either one of these confirms the diagnosis.Quantitative pilocarpine iontophoresis (sweat test) is the best initial test.
Chloride levels > 60 mmol/L on two or more occasions are consistent with CF.
The test should be conducted in patients > 2 weeks of age and > 2 kg in weight (more accurate).
Sweat test – this uses electrodes to provoke sweating. Two electrodes are placed on the skin, and a small current passed through them. Filter paper is used to collect a sample of the sweat. Then the concentration of both sodium and chloride ions is measured, but it is the chloride component that is important for diagnosis.
M:
Cystic fibrosis will be managed by the specialist MDT. There are many aspects to management:
Chest physiotherapy several times a day is essential to clear mucus and reduce the risk of infection and colonisation
Exercise improves respiratory function and reserve, and helps clear sputum
High calorie diet is required for malabsorption, increased respiratory effort, coughing, infections and physiotherapy
CREON tablets to digest fats in patients with pancreatic insufficiency (these replace the missing lipase enzymes)
Prophylactic flucloxacillin tablets to reduce the risk of bacterial infections (particularly staph aureus)
Treat chest infections when they occur
Bronchodilators such as salbutamol inhalers can help treat bronchoconstriction
Nebulised DNase (dornase alfa) is an enzyme that can break down DNA material in respiratory secretions, making secretions less viscous and easier to clear
Nebulised hypertonic saline
Vaccinations including pneumococcal, influenza and varicella
Other Treatment Options
Lung transplantation is an option in end stage respiratory failure
Liver transplant in liver failure
Fertility treatment involving testicular sperm extraction for infertile males
Genetic counselling
Ideally, management should be supervised by specialists in cystic fibrosis centers.
Respiratory
Hypertonic saline nebulization or aerosolized dornase alpha (recombinant DNAse that is a specific mucolytic agent that breaks down extracellular DNA in sputum)
Bronchodilator therapy (e.g., albuterol)
Chest physiotherapy
In chronic rhinosinusitis: intranasal glucocorticoids (see sinusitis)
Mucolytics (e.g., N-acetylcysteine)
High-dose ibuprofen has been shown to reduce respiratory disease progression.
In chronic respiratory insufficiency
Long-term oxygen inhalation therapy
Treatment of last resort: lung transplantation
Diet
Additional sodium chloride intake
High-energy diet to compensate for increased demand
Pancreatic enzyme supplements
Oral supplementation of lipophilic vitamins A, D, K, and E.
CFTR modulators.
Indication: patients with CF who are homozygous for the delta F508 mutation in the CFTR gene
Mechanism of action: These drugs modulate the expression of the defective CFTR protein by improving the production, intracellular processing, and function of the defective protein.
Combination therapy: The drugs work synergistically to increase both the quantity and function of the CFTR protein on the cell surface, resulting in enhanced chloride transport.
Drugs
Ivacaftor: improves Cl- transport by increasing the likelihood that the Cl- channel is open at the cell surface.
Combination therapy with either tezacaftor or lumacaftor
Lumacaftor: improves the conformational stability of the defective CFTR protein, which leads to increased intracellular processing and trafficking of functional CFTR protein to the cell surface
Tezacaftor: increases the amount of mature CFTR protein on the cell surface by improving intracellular processing and trafficking of the CFTR protein. Because CFTR modulators are only effective in patients with certain CFTR mutations, it is essential to perform CFTR genotyping prior to initiating treatment.
P:
cystic fibrosis trust gives a median life expectancy of 47 years.
90% of patients with CF develop pancreatic insufficiency
50% of adults with CF develop cystic fibrosis-related diabetes and require treatment with insulin
30% of adults with CF develop liver disease
Most males are infertile due to absent vas deferens
Meconium ileus
Definition: failure to pass the first stool in neonates (meconium usually passes in the first 24–48 hours after birth)
Etiology: Cystic fibrosis is the leading cause in (> 90%) of cases.
Clinical findings: signs of a distal small bowel obstruction
Bilious vomiting
Abdominal distention
No passing of meconium or stool
Diagnostics: abdominal x-ray (with contrast agent)
Dilated small bowel loops, microcolon, Neuhauser sign (“soap bubbles” effect)
Air-fluid levels are uncommon because of the viscous consistency of meconium.
Differential diagnosis: See differential diagnosis of intestinal obstruction in neonates.
Treatment
Enema with a contrast agent
Surgery is required in complicated cases: intestinal perforation or volvulus
Small bowel obstruction can also occur in older children and adults.
Hemoptysis
Allergic bronchopulmonary aspergillosis (ABPA): ∼ 10% of patients develop this condition.
Pulmonary emphysema
Pneumothorax
Cor pulmonale
The mainstay of treatment is symptomatic management. The median life expectancy is 39 years. Complications of chronic lung disease are the leading cause of death.
Prognosis
Median life expectancy: ∼ 39 years
The main determinant of life expectancy is the severity of pulmonary disease: chronic respiratory infections and mucus plugging → bronchiectasis (irreversible) → progressive respiratory failure → death
Progress in the medical and psychological management of patients with CF has lead to:
Significant improvement in survival in recent years
Successful pregnancies
Interstitial lung disease DR DEAC PIMP
D: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders marked by inflammatory changes in the alveoli. ILDs may be idiopathic or due to secondary causes such as autoimmune disease, pharmacotherapeutic changes, or exposure to toxic substances. These changes can cause irreversible fibrosis and impaired pulmonary function.
R: Age Exposure to occupational and environmental toxins: asbestos, astroesophageal reflux disease. ... Smoking. ... Radiation and chemotherapy. male sex, and older age.
D: cystic fibrosis? emphysema,
E: Incidence of all ILDs combined is about 30 per 100 000
Types of interstitial lung disease
Idiopathic pulmonary fibrosis
Poor prognosis – median survival 3-5 years. Typically older adults
Sarcoidosis
Usually good prognosis. Can affect younger adults
Pneumoconiosis
Variable prognosis depending on the cause
Drug induced ILD
Amiodarone, methotrexate
Hypersensitivity ILD
Usually has a good prognosis if the allergen is avoided
A: Idiopathic pulmonary fibrosis (IPF): most common
Risk factors: cigarette smoking, environmental or occupational exposures, chronic aspiration, genetic predisposition
Other idiopathic subtypes
Desquamative interstitial pneumonia (DIP)
Nonspecific interstitial pneumonia (NSIP)
Cryptogenic organizing pneumonia (COP)
Acute interstitial pneumonia (AIP) (an idiopathic, interstitial lung disease with an acute onset that can progress rapidly to respiratory failure)
Occupational, environmental, and iatrogenic causes
Pneumoconioses
Asbestosis
Silicosis
Rare pneumoconioses (e.g., berylliosis, anthracosis)
Radiation pneumonitis
Pharmacologic
Chemotherapeutic agents: bleomycin , methotrexate, busulfan
Other agents: amiodarone , nitrofurantoin, phenytoin, penicillamine, cocaine, and heroin
Secondary to underlying disease
Granulomatous ILD:
Sarcoidosis: noncaseating granulomas in multiple organs, including the lung
Pulmonary Langerhans cell histiocytosis
Granulomatosis with polyangiitis (formerly Wegener granulomatosis)
Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)
Infectious diseases (eg, tuberculosis, legionellosis)
Alveolar filling disease
Hypersensitivity reactions
Connective tissue disorders
Bronchoalveolar carcinoma
C: Main symptoms
Exertional dyspnea that progresses to dyspnea at rest
Persistent nonproductive cough
Fatigue
Other symptoms related to underlying primary disorder (eg, joint pain in connective tissue disorder)
Later stages of disease: digital clubbing due to chronic hypoxia
IPF: The majority of patients (> 70%) do not respond to therapy and experience progressive respiratory failure.
P:
I: Due to the wide variety of subtypes and symptoms, there is no generally recommended diagnostic algorithm. Physical examination, serology, pulmonary function tests, and imaging (chest x-ray , CT scan) is performed almost always, while lavage or biopsy depend on the individual case.
Auscultation
Bibasilar, inspiratory crackles or rales
In advanced pulmonary fibrosis: loud inspiratory squeaks
Signs of restriction: diaphragmatic elevation; sudden cessation of breathing on deep inhalation
Pulmonary function tests
Restrictive lung disease (e.g., low lung volumes, high/normal FEV1/FVC ratio)
Decreased diffusing capacity for CO (DLCO) → highly sensitive parameter
Chest x-ray
Normal in approximately 10% of patients.
Increase in reticular opacities (sign of fibrosis)
Ground-glass opacities and honeycombing
CT or HR-CT: Irregular thickening of the interlobular septa, honeycombing, and bronchiectasis
Biopsy
Indications: atypical or rapidly progressive symptoms
In patients with minimal signs or symptoms and stable disease, close observation (e.g., PFTs, HR-CTs over several months) may be sufficient.
Laboratory
Arterial blood samples show: elevated alveolar-arterial partial pressure of oxygen gradient, decreased partial pressure of oxygen
Screen for rheumatic and autoimmune diseases.
M: In secondary disease, the first step is to limit exposure to the toxic substance, cease therapy with the drug causing symptoms, or treat the underlying disease.
Antibiotics if bacterial interstitial pneumonia is suspected
Corticosteroids and immune modulators
Oxygen for symptomatic or end-stage ILD
Lung transplantation in end-stage ILD
Pirfenidone and nintedanib are commonly used medication for ILD.
P: prognosis is poor, esp for idiopathic.
Carcinoma of the bronchus
IOD?
Respiratory failure
type 1 resp failure (PaO2 < 8kPa) is relatively common. Treatment is with high-flow (60% oxygen). Transfer the patient to ITU if hypoxia does not improve with oxygen therapy or PaCO2 rises to greater than 6kpa. Be careful with oxygen in copd patients, check abgs frequently, and consider elective ventilation if rising paco2 or worsening acidosis. Aim to keep sao2 at 94-98%, pao2 greater than or equal to 8kpa.
Respiratory failure occurs when gas exchange is inadequate, resulting in hypoxia. It is defined as PaO2 smaller than or equal to 8kPa and subdivided into 2 types, according to PaCO2 level.
Type 1 respiratory failure: defined as hypoxia, <8kpa with a normal or low paco2. It is caused primarily by ventilation/perfusion (v/q) mismatch, hypoventilation, abnormal diffusion, right to left cardiac shunts. Examples of v/q mismatch: Pneumonia, pulmonary oedema, PE, asthma, emphysema, pulmonary fibrosis, ARDS.
Type 2 respiratory failure: hypoxia (PaO2 < 8kpa), with hypercapnia (PaO2 > 6.0kpa). This is caused by alveolar hypoventilation, with or without v/q mismatch. Causes include:
- Pulmonary disease: asthma, copd, pneumonia, end-stage pulmonary fibrosis, obstructive sleep apnoea.
- Reduced respiratory drive: sedative drugs, cns tumour or trauma.
- Neuromuscular disease: cervical cord lesion, diaphragmatic paralysis, poliomyelitis, myasthenia gravis, Guillain-Barre syndrome. Thoracic wall disease: flail chest, kyphoscoliosis.
Clinical features: those of the underlying cause together with symptoms and signs of hypoxia, with or without hypercapnia.
Hypoxia: Dyspnoea; restlessness; agitation; confusion; central cyanosis. If long standing hypoxia: polycythaemia; pulmonary hypertension; cor pulmonale. Hypercapnia: Headache; peripheral vasodilation, tachycardia, bounding pulse/tremor/flap; papilloedema; confusion, drowsiness, coma.
Investigations are aimed at determining the underlying cause:
• Blood tests: FBC, U&E, CRP, ABG.
• Radiology: CXR.
• Microbiology: sputum and blood cultures (if febrile).
• Spirometry (COPD, neuromuscular disease, Guillain–Barré syndrome).
Management depends on the cause:
Type I respiratory failure
• Treat underlying cause.
• Give oxygen (35–60%) by facemask to correct hypoxia.
• Assisted ventilation if PaO2 <8kPa despite 60% O2.
Type II respiratory failure: The respiratory centre may be relatively insensitive to
CO2 and respiration could be driven by hypoxia.
• Treat underlying cause.
• Controlled oxygen therapy: start at 24% O2. Oxygen therapy should be given
with care. Nevertheless, don’t leave the hypoxia untreated.
• Recheck ABG after 20min. If PaCO2 is steady or lower, increase O2 con centration to
28%. If PaCO2 has risen >1.5kPa and the patient is still hypoxic, consider assisted
ventilation (eg NIPPV, p823, ie non-invasive positive pressure ventilation). Rarely a
respiratory stimulant (eg doxapram 1.5–4mg/min IVI).
• If this fails, consider intubation and ventilation, if appropriate.
NICE guidelines for asthma management
-Add short-acting beta 2 agonist inhaler (e.g. salbutamol) as required for infrequent wheezy episodes.
-Add a regular low dose inhaled corticosteroid.
-Add an oral leukotriene receptor antagonist (i.e. montelukast).
-Add LABA inhaler (e.g. salmeterol). Continue the LABA only if the patient has a good response.
-Consider changing to a maintenance and reliever therapy (MART) regime.
Increase the inhaled corticosteroid to a “moderate dose”.
-Consider increasing the inhaled corticosteroid dose to “high dose” or oral theophylline or an inhaled LAMA (e.g. tiotropium).
Refer to a specialist.
Acute severe asthma
Severity of attack is underestimated.
An atmosphere of calm helps.
Presentation: acute breathlessness and wheeze.
Presentation Acute breathlessness and wheeze.
History (p48) Ask about usual and recent treatment; previous acute episodes and
their severity and best peak expiratory fl ow rate (PEF). Have they been admitted to ICU?
Diff erential diagnosis Acute infective exacerbation of COPD, pulmonary oedema,
upper respiratory tract obstruction, pulmonary embolus, anaphylaxis.
Investigations PEF—but may be too ill; arterial blood gases if saturations <92%; CXR
(if suspicion of pneumothorax, infection or life-threatening attack); FBC; U&E.
Assessing the severity of an acute asthmatic attack
Severe attack:
• Unable to complete sentences
• Respiratory rate >25/min
• Pulse rate >110 beats/min
• Peak expiratory fl ow 33–50% of predicted or best
Life-threatening attack:
• Peak expiratory fl ow <33% of predicted or best
• Silent chest, cyanosis, feeble respiratory eff ort
• Bradycardia or hypotension
• Exhaustion, confusion, or coma
• Arterial blood gases: •normal/high PaCO2 >4.6kPa (32mmHg)
•PaO2 <8kPa (60mmHg), or SaO2 <92%
•low pH, eg <7.35
Management: rapid treatment and reassessment.
Salbutamol 5mg nebulized with oxygen and give prednisolone 30mg PO.
If PEF remains <75%, repeat salbutamol; add ipratropoium.
Monitor oxygen saturation, heart rate and respiratory rate.
Admit all with severe features and not responding to initial treatment or with life-threatening features.
Discharge Patients, before discharge, must have:
• Been stable on discharge medication for 24h.
• Had inhaler technique checked.
• Peak fl ow rate >75% predicted or best with diurnal variability <25%.
• Steroid (inhaled and oral) and bronchodilator therapy.
• their own PEF meter and have management plan.
• GP appointment within 1wk.
• Respiratory clinic appointment within 4wks.
Drugs used in acute asthma
Salbutamol (2-agonist) SE: tachycardia, arrhythmias, tremor, K+
.
Hydrocortisone and prednisolone (steroid; reduces infl ammation)
Aminophylline is used much less frequently and is not routinely recommended in
current BTS guidelines, but may be initiated by respiratory team or ICU. It inhibits
phosphodiesterase; [CAMP]. SE: pulse, arrhythmias, nausea, seizures. The amount
of IVI aminophylline may need altering according to the individual patient: always
check the BNF. Monitor ECG.
• Factors that may necessitate reduction of dose: Cardiac or liver failure, drugs
that increase the half-life of aminophylline, eg cimetidine, cipro fl oxacin, erythromycin, contraceptive steroids.
• Factors that may require dose: Smoking, drugs that shorten the half-life, eg
phenytoin, carbamazepine, barbiturates, rifampicin.
Aim for plasma concentration of 10–20μg/mL (55–110μmol/L). Serious tox icity
(BP arrhythmias, cardiac arrest) can occur at concentrations ≥25μg/mL. Measure
plasma K+
: theophyllines may cause K+
. Don’t load patients already on oral preparations. Stick with one brand (bioavailability varies).
