COPD, Asthma, Bronchiectasis Flashcards
RF for COPD
Cigarette smoking
Pack years
Ave. no. of packs of cigarettes/day x total no. of years of smoking
Early onset COPD
genetic consideration
alpha 1 antitrypsin deficiency
Abnormal permanent enlargement of air spaces distal to the terminal bronchiole accompanied by destruction of walls of airways
Emphysema
Gene associated with COPD
HHIP Hedge hog interacting protein ch4
2 most important pathologic types of emphysema
Centriacinar emphysema
Panacinar emphysema
Central or proximal parts of the acini
Distal alveoli are spared
Consequence of cigarette smoking
Most common type
Centriacinar Centrilobular/Focal Emphysema
The acini are uniformly enlarged, from the level of respiratory bronchiole to the terminal blind alveoli
More common: lower lung zone
More common: a-1 antitrypsin deficiency
Panacinar (Panlobular) Emphysema
3 most common symptoms of COPD
Cough
Sputum production
Exertional dyspnea - increased effort to breathe, heaviness, air hunger or gasping
COPD PE
Prolonged expiratory wheeze Expiratory wheezing Signs of hyperinflation: barrel chest Use of accessory muscles Sitting in tripod position Cyanosis - lack of cyanosis in emphysema
Significant weight loss
Bitemporal wasting
Diffuse loss of subcutaneous adipose tissue
Hoover sign
Advance COPD
Independent poor prognostic factor in COPD
Bitemporal muscle wasting
Paradoxical inward movement of the rib cage with inspiration
Hoover sign
COPD Diagnostic
Pulmonary function testing
shows airflow obstruction with
dec FEV1
dec FEV1/FVC ratio
Hallmark of COPD
Airflow obstruction
Emphysema
Pinf puffer
Not cyanotic
Blue bloater
Chronic bronchitis
Persistent cough with sputum production for:
at least 3 months in
at least 2 consecutive years
Chronic bronchitis
Increased size of bronchial mucous glands (Reid index)
Squamous metaplasia of bronchial epithelium
Bronchiolar narrowing from mucous plugging
Inflammation and fibrosis
Chronic bronchitis
Increased size of bronchial mucous glands
Reid index
Ratio of thickness of mucous gland layer to the thickness of bronchial wall
Reid index
Current definitive test for establishing presence or absence of emphysema in living subjects
CT scan
Most important intervention in chronic bronchitis
Smoking cessation
Has been demonstrated to have a significant impact on mortality rate
Oxygen supplementation
In general, used for symptomatic benefit
B2 agonists
Bronchodilators
Improves symptoms and produces acute improvement in FEV
Decreases mucous secretions
Anticholinergics
Ipratropium bromide
Pharmacotherapy Emphysema
Beta agonist
Oral glucocorticoids
Antibiotics
GOLD Criteria for Severity of Airflow Obstruction
GOLD I
Mild
FEV1/FVC <0.7
FEV1 >/= 80% predicted
GOLD II
Moderate (50-80)
FEV1/FVC <0.7
FEV1 >/= 50% but <80% predicted
GOLD III
Severe (30-50%)
FEV1/FVC <0.7
FEV1 >/= 30% but <50% predicted
GOLD IV
Very severe
FEV1/FVC <0.7
FEV1 <30% predicted
Stable COPD Tx
Smoking cessation (Buproprion antidepressant, nicotine replacement therapy, varenicline)
Oxygen supplementation
Long acting beta 2 agonist
the only interventions proven to influence natural history of COPD
Syndrome characterized by airflow obstruction that varies markedly both spontaneously and with treatment
Asthma
Acute narrowing of bronchioles due to bronchospasm which causes obstruction to airflow maximal in expiration
Asthma
Risk factors in Asthma
Endogenous
Environmental
Triggers
Genetic predisposition Atopy Airway hyperresponsiveness Gender Ethnicity Obesity Early viral infections
Endogenous factors
Indoor allergens Outdoor allergens Occupational sensitizers Passive smoking Respiratory infections Diet Acetaminophen (paracetamol)
Environmental factors
Allergens Upper respiratory tract viral infections Exercise and hyperventilation Cold air Sulfur dioxide and irritant gases Beta blockers, Aspirin Stress Irritants (household sprays, paint, fumes)
Triggers
Single largest risk factor of Asthma
Atopy 40-50%
80% asthmatics have allergic rhinitis
Central to the disease pathophysiology and causes airway dysfunction through
inflammatory mediators
airway wall remodelling
Airway inflammation
asthma sputum cytology
Curschmann spirals
Eosinophils
Charcot-leyden crystals
Twisted mucous plugs admixed with sloughed epithelium
Results from extrusion of mucous plugs from subepithelial mucous gland ducts or bronchioles
Curschmann spirals
Eosinophil membrane proteins in asthma
Charcot-leyden crystals
Most striking gross finding in asthma
Occlusion of bronchi and bronchioles by thick, tenacious mucus plugs which often shed epithelium
Ciliated columnar cells sloughed from the bronchial linings
Creola bodies
Cough
Wheeze
Dyspnea
Inspiratory and expiratory rhonchi
Asthma
Most common stimuli that evoke asthma exacerbations
Infection
The only stimuli that can produce constant symptoms of asthma for weeks
Respiratory viruses
Young children: RVS, parainfluenza
Older children and adults: Rhinovirus, influenza
Abnormal and irreversible dilatation of the bronchial tree proximal to the terminal bronchioles
Bronchiectasis
Causes can be infectious or noninfectious
May be focal (bronchiectatic changes in a localized area of the lung) or Diffused (widespread bronchiectatic changes throughout the lung)
Bronchiectasis
Most common clinical presentation of bronchiectasis
Persistent, productive cough with
thick, tenacious sputum
Bronchiectasis hallmark
Honeycomb lung
Cystic spaces
Modality of choice for diagnosis of Bronchiectasis
Displays tram tracks
Bronchial wall thickening
Chest computed tomography (CT)
Bronchiectasis Tx
Treatment directed at control of
active infection
improvement in secretion clearance
bronchial hygiene
Bacterial infection implicated in severe asthma
Mycoplasma
Chlamydophila
Hypothesis proposes that lack of infection in early childhood preserves the TH2 cell bias at birth, whereas exposure to infections and endotoxin results in a shift towards a predominant protective TH1 immune response
Hygiene hypothesis
More severe persistent asthma
Later onset of disease
Nasa polyps
Aspirin-sensitive
Intrinsic or Non-atopic asthma
Most common allergen to trigger asthma
Dermatophagoides species
Dust mite
Exercise induced asthma is triggered by
Hyperventilation
Increased osmolality in airway lining fluid and triggers mast cell mediator release resulting in Bronchoconstriction.
Typically begins after exercise has ended
Recovers spontaneously within about 30 mins
Worse in cold, dry climates than in hot, humid conditions
More common in crosscountry running in cold weather, overland skiing and ice hockey
M
Exercise-induced asthma
Exercise-induced asthma is best prevented by
regular treatment with ICS (reduced mast cell)
prior administration if B2 agonist and antileukotriene
Asthma occurs more frequently in obese peopel with this value of BMI
more difficult to control
> 30kg/m2
A food additive and preservative that may trigger asthma through release of sulfur dioxide gas in the stomach
Metabisulfite
Physiologic abnormality of asthma
Airway hyperresponsiveness
Process allergen into peptides and migrate into lymph nodes and project these allergens into T cells to program allergen-specific T cells
Dendritic cells
Inflammatory cell linked to the development of airway hyperresponsiveness due to release of basic proteins and oxygen-deprived free radicals
Eosinophils
Which cytokine is deficient in asthma
IL 10 and 12 (antiinflammatory)
Mediate allergic inflammation: IL 4,5,9,13
Proinflammatory cytokines that amplify inflammatory response and play a role in more severe disease
TNF-a
IL-1B
Lung function test that demonstrates reversibilirt of airflow limitation
> 12% AND 200 mL increase in FEV1 15 mins after inhaled SABA (inhaled albuterol 400ug)
Or
2-4 week trial of oral corticosteroids (Prednisone or Prednisolone 30-40mg daily)
Confirms diurnal variation in airflow obstruction in asthma
PEF twice daily measurement
Flow-volume loop of asthma show
Reduced peak flow
Reduced maximum expiratory flow
Increased airway hyperresponsiveness in asthma with calculation of the provocative concentration that reduces FEV1 by 20%
Metacholine or histamine challenge
Chest Xray in asthmatics
Normal (in severe cases, hyperinflated lung)
Blood test not helpful
Skin prick test are positive in allergic asthma
Now being used as noninvasive test to measure eosinophilic airway inflammation
May be a test for compliance with therapy
Exhaled NO
Aims of asthma therapy
Minimal or no chronic symptom including nocturnal
Minimal infrequent exacerbation
No emergency visits
Minimally (ideally no) use of a required B2 agonist
No limitations on acitvities including exercise
Peak expiratory flow circadian variation <20%
Near normal PEF
Minimal or no adverse effect from medication
Drugs for asthma
Relievers - B2 agonist, anticholinergics, theophylline
Controllers -inhaled steroids, systemic steroids, leukotrienes, steroid sparing therapies, anti-IgE, Anti-IL5, immunotherapy
Activate Beta 2 adrenergic receptors in airways
Inc cAMP
Smooth muscle relaxation
Inhibits mast cell
Potential problem: tolerance
B2 agonists
SABA example
Duration: 3-6 hours
Albuterol
Terbutaline
LABA example
Should be given with ICS therapy
Salmeterol
Formoterol
Indacaterol
Olodaterol
Most common side effect of b2 agonist
Muscle tremor
palpitations
elderly
small fall in plasma sodium due to increasef uptake of skeletal muscle
Urinary retention from 10 year asthma medication use is caused by
Ipatropium
Anticholinergic
Prevent cholinergic nerve-induced bronchoconstriction and mucus secretion
Less effective than B2 agonist
Anticholinergics
SAMA example
Ipratropium
LAMA example
Tiotropium
Glycopyrronium
Most common SE of anticholinergic use
In the elderly
Dry mouth
Urinary retention and glaucoma
Inhibition of phosphodiesterase in airway smooth muscle cell
Inc cAMP causing smooth muscle relaxation
Anti-inflammatory effect
Theophylline
Key nuclear enzyme activated by theophylline that is a critical mechanism for switching off activated inflammatory genes and may reduce steroid insensitivity in severe asthma
Histone deacetylase 2 (HDAC2)
Increases blood concentration if theophylline
Erythromycin (inhibitor) Cimetidine Ciprofloxacin Allopurinol Zafirlukast
CHF, liver disease, pneumonia
Viral infection, vaccination
High carbohydrate diet
Old age
Increases clearance of theophylline
Inducers
Rifampicin
Phenobarbitone
Ethanol
High protein, low carbohydrate diet
Barbecued meat
Childhood
Most effective anti-inflammatory agent used in asthma therapy
Reduce eosinophils in the airways and sputum and activated T cells and mast cells in airway mucosa
First line therapy for patients with persistent asthma
Inhaled corticosteroids
Inhaled corticosteroid SE
Hoarseness
Oral candidiasis
Block cys-LT1 receptors by mast cells thereby causing bronchorelaxation
Modest clinical benefit in asthma
Given once or twice daily orally
Montelukast
Zafirlukast
Leukotriene inhibitors
Inhibit mast cell and sensory nerve activation
Effective in blocking trigger-Induced asthma such as EIA and allergen and sulfur dioxide-induced symptoms
Little benefit in long term control due to short duration of action
Cromones
Cromolyn sodium
Nedocromil sodium
Antibody that neutralized circulating IgE without binding to cell-bound IgE
Reduce the number of exacerbations in severe asthma
Very expensive
Only suitable for highly selected patients who are not controlled on maximal doses of inhaler therapy
Omalizumab
Reduce blood and tissue eosinophils and reduce exacerbations in patients with persistently increased sputum eosinophils despite maximal ICS therapy
IL 5
Daytime symptoms: None or = 2/week No limitation in activity No nocturnal symptom/awakening No or =2/week need for reliever/rescue treatment Normal lung function (PEF or FEV1)
Controlled
Daytime symptoms >2/week
Any limitation of activities
Any nocturnal symptom/awakening
Need for reliever/rescue treatment >2/week
Lung function (PEF1 or FEV1) <80% predicted or personal best if known
Partly controlled
> /= 3
Daytime symptoms >2/week Any limitation of activities Any nocturnal symptom/awakening Need for reliever/rescue treatment >2/week Lung function (PEF or FEV1)
Uncontrolled
ABG picture consistent with impending respiratory failure
ph 7.4, pCO2 40, PaO2 80, HCO3 35
Hpoxemia and PCO2 usually low due to hyperventilation
But a normal or rising PCO2 is an INDICATION OF IMPENDING RESPIRATORY FAILURE and requires immediate monitoring and therapy.
Laboratory test to confirm compliance to asthma therapy
Fractional NO may identify adherence to ICS
Type of asthma that presents with chaotic variations in lung function despite appropriate therapy and may have precipitous, unpredictable falls in lung function which may result in death
Generally normal of near-normal lung function but precipitous, unpredictable falls may result in death
Difficult to manage
Type 2 brittle asthma
Chaotic variations in lung function despite taking appropriate therapy. Persistent pattern of variability and may require OCS or at times, continuous infusion of B2 agonist
Type I Brittle asthma
Brittle asthma Tx
Subcutaneous Epinephrine
localized airway anaphylactic reaction with edema
1/3 improve during the course of pregnancy
1/3 deteriorate
1/3 remain unchanged
Drugs that are safe and without teratogenic potential
Asthma and pregnancy
Drugs that are safe and without teratogenic potential in pregnants with asthma
SABA, ICS and theophylline
Prednisone»_space; Prednisolone
Mosy common form of bronchiectasis
Cylindrical/tubular
Varicose/cystic
Bronchiectatic changes in a localized area of the lung and can be consequence of obstruction of the airway - either extrinsic (lymphadenopathy, parenchymal tumor) or intrinsic (airway tumor, aspirated body, stenotic airway)
Focal bronchiectasis
Widespread bronchiectatic changes throughout the lung and often rises from an underlying systemic or infectious disease process
Diffuse bronchiectasis
Upper lung field bronchiectasis may be due to
More common
Cystic fibrosis
Post radiation fibrosis
Lower lung field bronchiectasis may come from
Chronic recurrent aspiration
End-stage fibrotic lung disease
Recurrent immunodeficiency association
Causes bronchiectasis in midlung fields
Mycobacterium avium intracellulare complex
Dyskinetic/immotile cilia syndrome (Kartegener)
Bronchiectasis of central aways is due to
Allergic bronchopulmonary aspergillosis
Tracheobronchomegaly
(Mounier-Kuhn Syndrome and Williams-Campbell syndrome)
Most widely cited mechanism of infectious bronchiectasis that states that susceptibility to infection and poor mucociliary clearance result in microbial colonization of the bronchial tree
Vicious cycle hypothesis
Dilated airways arising from parenchymal distortion as a result of lung fibrosis (eg. postradiation fibrosis or idiopathic pulmonary fibrosis)
Traction bronchiectasis
Crackles and wheezing
Clubbing of digits
PFT: mild to moderate airflow obstruction
Acute exacerbation: Changes in the nature of sputum production with increased volume and purulence
Bronchiectasis
Bronchiectasis Xray reveal
Tram tracks indicating dilated airways
Cross sectional area of the airway with a diameter of at least 1.5 times that of the adjacent vessel in CT
Bronchiectasis
Signet ring sign
Inspissated secretions on CT of a bronchiectatic lung
Tree-in-bud appearance
Cyst eminating in a bronchial wall in cystic bronchiectasis
Diagnosis of a true non-tuberculous mycobacterial infection in a patient with bronchiectasis is seen in
One bronchioalveolar lavage sample positive on culture
Diagnostic criteria for true clinical infection with NTM should be considered in patients with symptoms and radiographic findings of lung disease who have at least 2 sputum samples positive on culture.
At least one BAL fluid sample postive on culture
A biopsy sample displaying histopathologic features of NTM infection (granuloma, positive stain for acid-fast bacilli) along with one positive sputum culture
Pleural fluid sample (or a sample from another sterike extrapulmonary site) positive
Most common nontuberculous mycobacterial pathogens implicated in bronchiectasis
M avium-intracellulare
Tx:
HIV negative - Macrolide + Rifamin + Ethambutol
Check macrolide susceptibility testing
Bronchiectasis Tx
Antibiotic treatment
Bronchial hygiene (Pulmonary rehabilitation)
Anti-inflammatory therapy (OCS/systemic steroids)
Surgical interventions for refractory cases
Prevention of bronchiectasis
Reversal of an underlying immunodeficient state - IVIg
Vaccination -influenza, pneumococcal
Smoking cessation
Complications of bronchiectasis
Microbial resistance to antibiotics
Injury to superficial mucosal vessels with bleeding -> life threatening hemoptysis
Endotracheal intubation
Identification of source of bleeding
Control of bleeding - bronchial artery embolization, surgery
Decline rate of FEV1 among patients with non-CF bronchiectasis
50-55 ml per year
Worse outcomes in bronchiectasis are associated with this infection
P aeruginosa colonization
Disease state characterized by persistent respiratory symptoms and airflow limitation that is not fully reversible
COPD
Noxious environmental exposures by spirometry in setting of noxious exposure eg cigarette smoking
Chronic airflow obstruction
COPD
Subset of COPD
Emphysema
Chronic bronchitis
Small airway disease
A condition characterized by destruction of the lung alveoli with airspace enlargement
Emphysema
A clinically defined condition with chronic cough and phlegm
Chronic bronchitis
Condition in which small bronchioles are narrowed and reduced in number
Small airway disease
Hallmark of advanced COPD
Extensive small airway destruction
Small airways may be narrowed by cells (hyperplasia and accumulation), mucus, and fibrosis
The elastase:antielastase hypothesis was based on the clinical observation that patients with genetic deficiency of this substance were at increased risk of emphysema
a-1 anti trypsin
Elastase > Anti-elastase (a1 antitrypsin)
Major site of increased resistance in most individuals with COPD
Small airways <2mm diameter
Associated with significant airway inflammation and with centrilobular emphysema
Along the pleural margins with relative sparing of the lung core or central regions
Paraseptal emphysema
Lung hyperinflation among patients with COPD indicate
Increase in lung volume (inc RV, inc RV/TLC)
Increase in elastic recoil pressure (inc TLC)
Decrease airway resistance
Hypoxemia in COPD is caused by
ventilation-perfusion mismatch
reflects heterogenous nature of disease process
multiple parenchymal regions with different v/q
Dec PO2
Shunting at minimal rate
Most highly significant predictor of FEV1 among COPD patients
Pack-years of cigarette smoking
But only 15% of the variability in FEV1 is explained by pack-years
70/Male
Ex smoker
FEV1/FVC <0.7
FEV >80% predicted
GOLD Criteria?
GOLD stage I
Only 3 interventions demonstrated to improve survivals of patients with COPD
Smoking cessation
Oxygen therapy
Lung volume reduction surgery
Only pharmacologic therapy demonstrated to unequivocally decrease mortality rates in patients with COPD
Supplemental O2
Patient with resting hypoxemia
Resting O2 saturation =88% in any patient
= 89% with signs of pulmonary hypertension or right heart failure
Type of infection most associated with COPD exacerbation
Bacterial
Hib
Antibiotic that has demonstrated a reduced exacerbation of frequency and longer time to first exacerbation
Azithromycin
COPD patients most likely to benefit from lung volume reduction surgery
Those with upper lobe-predominant emphysema and a low post-rehabilitation exercise capacity
Most emphysematous portion of lung
Reduce the length of hospital stay, hasten recovery, and reduce the chance of subsequent exacerbation or relapse among admitted COPD patients
Systemic corticosteroids
70/F
Known smoker, COPD
Dyspnea at rest
Productive cough with yellowish sputum
What makes her unfit for noninvasive positive pressure ventilation
a able to expectorate secretion
b being obtunded
c able to cooperate
d normotensive SBP 120 mmHg
Being obtunded
Contraindications for Non invasive Positive-Pressure Ventilation (NIPPV)
Cardiovascular instability
Impaired mental status
Inability to cooperate
Copious secretions or inability to clear secretions
Craniofacial abnormalities or trauma precluding effective fitting of mask
Extreme obesity
Significant burns
Indications for Invasive Mechanical Ventilation
Severe respiratory distress despite therapy Life-threatening hypoxemia Severe hypercarbia and/or acidosis Markedly impaired mental status Respiratory arrest Hemodynamic instability
