pulmonolgy2 Flashcards
pneumonia
is an infection of the lung parenchyma. Clinically, pneumonia is classified a community- acquired (CAP), which refers to an infection acquired outside of hospitals or extended-care facilities. Health-care associated (HCAP) includes patients who have recently been hospitalized within 90 days of the infection, resided in a nursing home or long-term care facility, or received parenteral antimicrobial therapy, chemotherapy, or wound care within 30 days of pneumonia. Despite the multiplicity of antibiotics available for treat the disease, pneumonia remains a leading cause of death in the United States (7th). Hospital-acquired (HAP) pneumonia is defined as pneumonia that occurs 48 hours or more after hospital admission and that was not present at the time of admission. Ventilator Associated pneumonia (VAP) refers to pneumonia that occurs 48 hours or more after endotracheal intubation. The incidence of CAP is 4-5million/year with nearly 25% requiring hospital admission. Health-care and hospital acquired pneumonias are estimated to occur in 250,000 persons/year and represent 15-20% of all nosocomial infections. The term HAP is often used to represent both VAP and HCAP. For practical purposes, most principles for HAP, VAP, and HCAP overlap.
Pathogenesis of Pneumonia
Mechanisms have been identified in the pathogenesis of pneumonia in immunocompetent adults include inhalation of infectious particles, inhalation of oropharngeal or gastric contents, hematogenous spread, infection from adjacent or contiguous structures, direct inoculation and reactivation. Inhalation of infectious particles is probably the most important pathogenic mechanism in the development of community-acquired pneumonia, with particular importance of pneumonia caused by Legionella species and M. tuberculosis. Pneumonia occurs when the host’s ability to fight against invading microbial pathogens is compromised. The reduced state of the immune system could be due to interplay amongst different host factors, including underlying comorbidities, immunosuppressive medications, and a depressed level of consciousness leading to impaired mechanical (ciliated epithelium and mucus), humoral, and cellular host defenses.
Clinical evaluation of pneumonia
Initial evaluation involves history, physical exam and radiographic testing. Diligent history taking can direct the differential diagnosis of infectious agents. Clinical diagnosis of pneumonia requires clinical evidence of pulmonary parenchymal inflammation due to infection (bacterial, fungal, viral) in which purulence develops and fills the alveoli. Common clinically signs and symptoms include fever, chills, pleuritic chest pain, dyspnea and cough that can productive of sputum (bacterial infections) or with minimal sputum (atypical vs viral). Other clinical features include anorexia, nausea+/- vomiting, diarrhea, mental status changes. On physical exam, patients are typically febrile (>80%), with tachypnea and tachycardia. Lung exam can reveal crackles, rhonchi and bronchial breath sounds. If there is evidence of consolidation, patients will have egophony and dullness to percussion. The absence of these physical exam findings does not exclude pneumonia. The vast majority of patients will have leukocytosis with a left shift. Leucopenia, if concurrent with a diagnosis of pneumonia, portends a poor prognosis
Radiographic Evaluation of pneumonia
The presence of infiltrates on a plain chest x-ray with the appropriate clinical and microbiologic features is considered the gold standard for diagnosis. Chest x-ray should be obtained on all patients for which pneumonia is suspected. The radiographic features of pneumonia include: Lobar consolidation, Interstitial infiltrates, and caviation. Radiographic features alone cannot differentiate etiology of pneumonia and radiographic abnormalities is not sufficient to confirm the diagnosis of pneumonia by itself. In the absence of clinical or microbiologic supportive evidence of pneumonia the differential
diagnosis includes: Pulmonary edema, Pulmonary or diffuse alveolar hemorrhage, Pulmonary embolism, Malignancy, Drug induced lung disease, Inflammation secondary to non-infectious causes. Alternatively, if plain x-ray does not support the clinical suspicion, advanced radiographic testing can be ordered (CT chest), as CT is clearly superior to plain radiographs are detecting lesions and defining the anatomical position of pneumonia. Clinical situation in which plain radiographs may be initially negative include volume depletion and patients who are immunocompromised. CT scan to diagnosis pneumonia is not generally recommended as it incurs higher cost and has not been shown to improve outcomes.
Initial Management
Once pneumonia is diagnosed, the next critical decision includes determining indication for hospital admission. The Patient Outcome Research Team (PORT) study determined an validated a risk scale, Pneumonia Severity Index to help guide decision making regarding severity of CAP and indications for admission (risk class IV and V).
Diagnostic Testing
In patients who are not severely ill and have few risk factors, consensus guidelines from the IDSA/ATS recommend empiric treatment without additional testing. At minimum, all patients with suspected pneumonia should have the following: chest radiograph, complete blood count, complete metabolic profile, and blood gas or pulse oximetry. Advanced testing is reserved for individual clinical situations. Blood cultures can also shed light on a pathogen, and samples should be drawn in severely ill or immunocompromised patients. Pleural or cerebrospinal fluid should be sampled when infections in these spaces are suspected.
Gram staining for pneumonia
Gram-stained sputum specimen can help focus empiric antibiotic therapy. Sputum samples can be difficult to obtain from older patients because of a weak cough, obtundation, and dehydration. Nebulized saline treatments might help mobilize secretions. Nasotracheal suctioning can sample the lower respiratory tract directly but risks oropharyngeal contamination. A sputum specimen reflects lower respiratory secretions when more than 25 white blood cells (WBCs) and fewer than 10 epithelial cells are seen in a low-powered microscopic field. Other stains, such as the acid-fast stain for mycobacteria, modified acid-fast stain for Nocardia, or toluidine blue and Gomori’s methenamine silver stains should be used when directed by the history or clinical presentation. Direct fluorescent antibody (DFA) staining of sputum, bronchoalveolar lavage fluid, or pleural fluid can help identify bacterial infections (Legionella species) as well as rapid diagnosis of viral infections (nasopharyngeal DFA swab for influenza types A and B), as well as other common respiratory viruses such as respiratory syncytial virus, adenovirus, and parainfluenza virus. The sputum culture can be used to help tailor therapy
in certain clinical situations (admission to ICU, failure of
antibiotic therapy, cavitary lesions, alcohol abuse, structural
lung disease, immunocompromised host, pleural effusion,
epidemic pneumonia). Culture is particularly helpful for identifying organisms of epidemiologic significance, either for patterns of transmission or resistance. Expectorated morning sputum specimens should be sent for mycobacterial culture when the history is suggestive.
Bronchoscopy for diagnosis of pneumonia
When these procedures fail to yield a microbiologic diagnosis and when the patient does not respond to empirical antibiotic therapy, more-invasive diagnostic techniques may be indicated. Fiberoptic bronchoscopy allows the use of several techniques for the diagnosis of pneumonia. Bronchoalveolar lavage with saline can obtain deep respiratory specimens for the gamut of stains and cultures mentioned earlier. Transbronchial biopsy of lung parenchyma can reveal alveolar or interstitial pneumonitis, viral inclusion bodies, and fungal or mycobacterial elements. The protected brush catheter is used to distinguish quantitatively between tracheobronchial colonizers and pneumonic pathogens. A more substantial amount of lung tissue may be obtained for culture and histologic examination by thoracoscopic or open lung biopsy. Because these procedures can carry considerable morbidity, they are usually reserved for the deteriorating patient with a pneumonia that defies diagnosis by less-invasive techniques.
Serologic Testing
Serologic testing for such pathogens as Legionella species, Mycoplasma species, and C. pneumoniae should include sera drawn in the acute and convalescent phases for comparison. A fourfold increase in the immunoglobulin G (IgG) titer suggests recent infection with these organisms. An IgM microimmunofluorescence titer of more than 1:16 is considered diagnostic of C. pneumoniae infection. Infection with SARS-associated coronavirus is most often diagnosed by antibody testing and polymerase chain reaction (PCR) testing. A sensitive enzyme immunoassay has been developed for the detection of L. pneumophila type 1 antigen in urine, however, the antigen can persist for up to 1 year after infection, making it difficult to differentiate between past and current infections when using this assay. A urinary assay is also available for detecting S. pneumoniae cell wall polysaccharide. This assay may offer some advantage for the rapid diagnosis of pneumococcal pneumonia in culture-proven or unknown cases, but assay specificity is an ongoing question.
Molecular Techniques for pneumonia diagnosis
Powerful molecular techniques are now being applied to the early diagnosis of pneumonia. DNA probes have been used to detect Legionella species, M. pneumoniae, and M. tuberculosis in sputum. These probes have excellent sensitivity and specificity but can yield false-positive results. The PCR assay has been used for the early detection of various pathogens that are difficult or slow to culture from sputum specimens, including atypical bacteria, viruses (e.g., influenza), and mycobacteria. Given the large percentage of pneumonia cases for which no microbial cause is identified, it is likely that molecular tools will eventually be applied to the identification and antimicrobial susceptibility testing of almost all causative agents of pneumonia.
Procalcitonin
a peptide precursor of the hormone calcitonin. It is produced parecnchymal cells in response to bacterial toxins. The level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (10pg/mL) of clinical assays. The level of procalcitonin rises in a response to a proinflammatory stimulus, especially of bacterial origin, and is produced mainly by the cells of the lung and the intestine. It does not rise significantly with viral or non-infectious inflammations. In serum, procalcitonin has a half-life of 25 to 30 hours. Remarkably the high procalcitonin levels produced during infections are not followed by a parallel increase in calcitonin or a decrease in serum calcium levels. In severe infection with clinical evidence of severe sepsis, the blood levels of procalcitonin may rise to 100 μg/L and has a sensitivity of 76% and specificity of 70%. In a Cochrane meta-analysis, procalcitonin level was found to be helpful in guiding when to use antibiotic therapy, use of antibiotics was more or less discouraged (
Antibiotic Treatment for pneumonia
Antibiotic therapy for CAP should be directed using patient characteristics, severity of disease and epidemiologic traits. Concerns about antimicrobial overuse, health care costs, and bacterial resistance increasing, therapy should follow confirmation of the diagnosis of pneumonia and should always be accompanied by a diligent effort to identify a causative agent. When a specific pathogen is identified, pathogen- specific therapy can be used. Most cases of pneumonia are adequately treated with 10 to 14 days of antibiotics. Longer courses may be required for certain organisms that cause tissue necrosis, (e.g., Legionella spp., S. aureus, Pseudomonas aeruginosa), organisms that live intracellularly (e.g., C. pneumoniae), or comorbidities that compromise local (COPD) or systemic (hematologic malignancy) immunity.
Pneumonia Prevention
Immunization against influenza and increasingly resistant pneumococci can play a critical role in preventing pneumonia, particularly in immunocompromised and older adults. The influenza vaccine is formulated and administered annually. The Centers for Disease Control and Prevention (CDC) recommends that vaccines be offered to persons older than 50 years, residents of extended-care facilities, and patients who have chronic heart and lung disorders, chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression. The pneumococcal vaccine has been shown to be 60% to 70% effective in immunocompetent patients. Side effects are rarely serious and consist of local pain and erythema, which occur in up to 50% of recipients. The CDC recommends that vaccines be offered to all persons 65 years of age or older, those at increased risk for illness and death from pneumococcal disease because of chronic illness, those with functional or anatomic asplenia, and immunocompromised persons. Patients who are immunosuppressed by chronic disease or treatment might not have sustained titers of protective antibody and should be considered for revaccination after 6 years.
Residual immunity against Bordetella pertussis wanes over time, leading to transmission from older adults to other adults and infants. Because secondary bacterial pneumonia occurs in a significant number of cases of pertussis, the ACIP (Advisory Committee on Immunization Practices) has recommended that the tetanus-diphtheria-acellular pertussis (Tdap) vaccine replace the tetanus-diphtheria (Td) vaccine in the adult immunization schedule.
Influenza
An acute respiratory illness that is caused by either influenza A or B virus. Occurs as outbreaks and epidemics in a seasonal variation (winter season). Signs and symptoms of active infection include systemic illness (i.e. headache, myalgias, weakness) and upper and lower respiratory tract involvement. In the general population, influenza is a self-limiting though debilitating disease; however in certain at risk populations, it is associated with increased morbidity and morality.
Epidemiology of Influenza
Distinct outbreaks occur yearly with a seasonal distribution (winter) and reflect the changing nature of the antigenic properties of the virus. Mutliple strains of IFN typically ciruculate during a season. Of the IFN viruses, IFN A virus easily undergoes changes in the antigenic characteristics of their envelope glycoproteins. Outbreaks occur over a 2-3 week time period and last 2-3 months. Most outbreaks affect between 10-20% of the general population, but high rates can be seen in at risk persons.
Pathogenesis of Influenza
Transmission requires close contact with an infected individual via exposure to respiratory secretions (sneezing, cough). Close contact is required as the virus is large (>5 microns) and does not remain airborn for distances greater than 6 feet. IFN viral incubation period is 1-4 days with onset of illness occurring within 3-4 days. The virus can ‘shed’ from infected individuals 24-48 hours prior to onset of illness and continue for as long as 10 days, though the titers drop dramatically during symptomatic illness. At risk populations (children, aged adults, patients with chronic illness and immunocompromised hosts) have been shown to shed for up to 3 weeks. The pathogenic nature of influenza is related to the antigenic changes in it’s hemagglutinin, which is a surface glycoprotein that binds to sialic acid residues on respiratory epithelial cell surface glycoproteins and starts the infection. As the virus reproduces, the virions are also bound to the host cell. Neuraminidase cleaves these links and liberates the new virions; it also counteracts hemagglutinin-mediated self-aggregation entrapment in respiratory secretions. Among influenza A viruses that infect humans, three major subtypes of hemagglutinins (H1, H2, and H3) and two subtypes of neuraminidases (N1 and N2) have been described. Influenza B viruses have a lesser propensity for antigenic changes, and only antigenic drifts in the hemagglutinin have been described.
Clinical Features of Influenza
Uncomplicated Influenza occurs as an abrupt onset of fever, headache, myalgias and malaise. It can be associated with URI symptoms such as cough, nasal congestion and sore throat. Physical exam findings are include pharyngeal hyperemia and lymphadenopathy. This constellation of signs/symptoms are often confused with the common cold. Treatment is supportive.
Several complications can follow influenza viral infection
Pneumonia: The most common complication and occurs in patients who are high risk. The types of pneumonia that are encountered are
categorized as primary viral pneumonia, secondary bacterial
pneumonia, or a mixture of both. Primary influenza
pneumonia is the most clinically severe, but the least
common, of the pneumonic complications of influenza. It has
an apparent predilection for individuals who have elevated
left atrial pressures, although it has also been described in
patients with chronic pulmonary disorders and rarely in apparently otherwise healthy young adults. Secondary bacterial pneumonia contributes substantially to morbidity and mortality, and is common in individuals ≥65 years of age. The clinical hallmark of the clinical presentation in patients with secondary bacterial pneumonia recurrence of pulmonary symptoms after initial improvement in the symptoms of acute influenza. Mouse models of synergism between influenza virus and S. pneumoniae, the level of activity of neuraminidase correlated with increased adherence and invasion of S. pneumonia. The most common bacterial pathogen is Streptococcus pneumonia, Staphylococcus aureus, and Haemophilus influenza.
Myositis and rhabdomyolysis
an important complications of and occurs most frequently in children. Although myalgias are a prominent feature of most cases of influenza, true myositis is uncommon. The pathogenesis of the myositis is not well understood. The hallmark of acute myositis is extreme tenderness of the affected muscles, most commonly in the legs. In the most severe cases, swelling and bogginess of the muscles may be noted. Markedly elevated serum creatine phosphokinase concentrations can be seen.
Central nervous system
may be associated with influenza, including encephalopathy, transverse myelitis, aseptic meningitis, and Guillain-Barré syndrome. However, the pathogenesis of the CNS illnesses associated with influenza remains poorly understood.
Cardiac complications
include electrocardiographic changes, increased risk of MI, myocarditis and pericarditis. The latter two are rare.
Treatment of Influenza
Indications include illness requiring hospitalization; progressive, severe or complicated illness; and those at risk (see Table 7). Treatment should be given within 48 hours of illness. Treatment includes neuroaminidase inhibitor (oseltamivir or zanamivir). Assess risk of oseltamivir resistance by reviewing the state influenza data as H1N1 IFN A has been reported. The adamantanes are no longer indicated given the high rates of resistance.
Restrictive disease
the complement of obstructive disease. The compliance of the lung is reduced, while the airway resistance is reduced. Gas exchange abnormalities may result from both ventilation-perfusion (V/Q) mismatch and diffusion abnormalities. Remember that the total pressure to begin airflow in the respiratory system is: Ptot = Pel + Pr. Ptot = the total pressure. Pel = pressure required to overcome elastic recoil of the lung. Pr = pressure required to overcome the resistance to airflow. Obstructive disease primarily increases resistive pressure, Pr. Restrictive disease increases the work required to distend the lung, the Pel. The respiratory system is composed of both the lung and the chest wall in series.
compliance (C)
is the (change in volume)/(change in pressure). (This is the inverse of elastance.) 1/Ctot = 1/Clung + 1/Ccw. Ctot = Compliance of the total system. Clung = Compliance of the lung. Ccw = Compliance of the chest wall. The compliance of the lung and chest wall separately is about 0.2L/cmH20. But combined the compliance is half that: 0.1 L/cm H20. This occurs because of the counterbalancing recoil forces of the chest wall and lung. The principle is that compliance of the respiratory system may be affected by changes in compliance of either the chest wall or lung (or both). Also keep in mind that the pressure-volume (P-V) curve is not linear, and thus compliance represents a point estimate for any given lung volume. This is the reason that the curve is shown for values across the patient’s vital capacity. Clinically, the pressure volume curve is measured by inserting an esophageal pressure monitor that is a surrogate for pleural pressure. This allows for measurement of the difference that transpulmonary pressure has on lung volume. Transpulmonary pressure is the difference between the pressure applied to the airway and the pressure in the pleural space. The result is a pressure volume curve for the lung alone.
Mechanisms that change lung compliance
A decrease in lung compliance can occur via 3 mechanisms: 1. Increased thickness of the lung interstitium. 2. Increased lung water. 3. Increased alveolar surface tension. Increases in the thickness of the interstitium can occur from many causes. There is increased deposition of elastic/connective tissue in many forms of chronic interstitial lung disease. In response to an injury, lung fibroblasts produce excessive collagen and elastin in the alveolar walls. This abnormal proliferation causes an increase in interstitial matrix which increases the elastic recoil of the lung and essentially stiffens the lungs. An increase in inflammatory cells in the interstitium can similarly stiffen the lung. Increased lung water is most commonly seen with congestive heart failure: initially fluid escapes the capillary and fills the interstitium (which thickens the interstitium and increases elasticity. Next, fluid fills the alveoli which disrupts the surfactant and increases surface tension.
Respiratory distress syndrome
Increases in alveolar surface tension tend to cause alveoli to collapse and remain closed which reduces compliance. Dilution of the normal surfactant via cardiogenic or noncardiogenic pulmonary edema (increased lung water) can increase surface tension. Abnormalities in surfactant production or functionality can also increase surface tension. Respiratory distress syndrome (formerly, hyaline membrane disease) in premature infants is a result of inadequate surfactant production due to immature lung development. In adults, a form of acute lung injury called acute respiratory distress syndrome (ARDS) results in dysfunctional surfactant due to injury to type 2 alveolar cells; furthermore noncardiogenic pulmonary edema in this disorder dilutes the surfactant that is present. ARDS also results in inflammation and injury in the interstitium that decreases compliance.
Pressure volume curve of normal and diseased states
TLC, FRC and RV are all decreased in pure restrictive lung disease. The PV curve is flatter and shifted down (reflecting lower lung volumes) as shown by this curve for pulmonary fibrosis. In patients with acute pulmonary edema (either due to heart failure or ARDS) P-V curves are usually not measured but would look the same as for fibrosis. Static compliance is easily measured in mechanically ventilated patients by measuring the pressure required to inflate a patient’s lung to a certain volume.
Supranormal airflow
Remember that peak expiratory lung flow is determined by lung volume. Airflows in pulmonary fibrosis and other forms of interstitial lung diseases are supranormal for a given lung volume because the airways are dilated due to traction applied from adjacent parenchyma. This phenomenon is termed traction bronchiectasis. For any given lung volume, the airflows will be higher than expected. The figure at left shows typical flow volume loops. Note that lung volumes must be measured to plot this graph. Spirometry will show a normal or elevated FEV1/FVC ratio. Resistance = 8nl/(πr4), where n = viscosity, l = length, r = radius.
Diffusion abnormalities
Restrictive disease due to various interstitial lung diseases results in impaired gas-exchange. This results from a decrease in lung volumes with subsequent decrease in alveolar capillary surface area. Diffusion can also be impaired as the thickness of the alveolar-capillary wall increases. The diffusion abnormality becomes more pronounced with exercise as the transit time across a capillary decreases from an average of 0.75 seconds to as short as 0.25 seconds. Symptoms with exercise are usually the earliest manifestation of interstitial lung disease. Ventilation-perfusion abnormalities also contribute to gas exchange abnormalities in restrictive disease. A decrease in diffusing capacity (DLCO) is often the first abnormality in patients with restrictive disease. DLCO can be corrected for alveolar volume (VA) to account for the decrease in diffusing capacity that results from reduced lung volumes. Be careful: many restrictive diseases result in lower lung volumes AND impair the function of the alveolar capillary membrane. A decreased DLCO that normalizes for VA should not suggest the absence of parenchymal lung disease.
Mechanisms that change chest wall compliance
Disease in any compartment of the chest wall from the skin to the pleura can result in decreased compliance of the chest wall system and a restrictive pattern. Some examples: burns: third degree burns form a thick eschar that limits chest wall excursion obesity- increases soft tissue mass and decreased ability of the chest wall to move kyphoscoliosis- deformity of the spine (lateral and anterior displacement) ankylosing spondylitis- inflammatory disease which causes ossification of the ligamentous structures of the spine (the bamboo spine). This restricts movement of the ribs respiratory muscle weakness - paralysis of the muscles, neuromuscular disease pleural fibrosis/thickening- restricts expansion of the lung within the thoracic cavity. pleural effusion - fluid in pleural cavity limits lung expansion
Abnormalities of the chest wall
Abnormalities of the chest wall lead to decreased lung volumes (including FRC) and normal airflow. Restrictive disease due to chest wall or pleural disease does not alter the function of the gas-exchange at the alveolar capillary membrane. As noted above, a mild reduction in lung volumes reduces the DLCO because the total surface area of the alveolar capillary membrane is reduced, but this corrects when DLCO is corrected for alveolar volume (DLCO /VA). At lower lung volumes, however, the lung develops regional atelectasis and other V/Q mismatch that can occur with ventilation at low lung volumes.
Pulmonary problems due to muscular weakness
In patients with muscular weakness, the effort dependent PFT measurements are affected but FRC is normal (low TLC and increased RV). This pattern is also seen in persons who put forth a poor effort (either on purpose or do not understand what they are supposed to do). The P-V curve of the lung can help distinguish between chest wall and muscular disease from restrictive lung diseases (fibrosis, edema). In patients with chest wall and/or muscular diseases, the slope of the P-V curve will be normal but the lung volumes (TLC) will be lower.
How do you determine whether restrictive physiology is due to obesity (chest wall) or due to interstitial lung disease?
Restrictive physiology caused by intrinsic lung disease can be distinguished from that caused by chest wall pathology by history, physical exam, chest radiograph, diffusing capacity, and pressure-volume curve. Pressure-volume curves can be used to assess the compliance of the lung without the effects of the chest wall. To review, a manometer is passed into the mid-esophagus which gives a close estimation of pleural pressure. In the body box a patient exhales slowly from TLC and lung volumes are measured periodically using Boyle’s Law. The volume is correlated to the pleural pressure as determined by the esophageal manometer. Since the manometer is inside the chest wall and (almost) directly measuring pleural pressure any restrictive effects of the chest wall are eliminated. Above are examples of P-V curves in these states. Obesity moves the curve down and to the right, but the shape of the curve (aka. the slope of the curve) mirrors that of the normal. Fibrosis flattens the curve (i.e. decreased the slope) and shows that increases in pressure result in decreased changes in volume compared to normal. People can have obstructive disease, restrictive disease, or a combination of both.
Examples of patients with a mixed disorder
An obese patient with asthma, Combined pulmonary fibrosis and emphysema, A construction worker with interstitial lung disease from asbestos or silica exposure who also has α1- antitrypsin deficiency. These people can have various PFT’s, but a classic scenario would be a decrease in TLC or FRC (restrictive) with a decreased FEV1/FVC (obstructive). Usually the combination of disorders combines to markedly decrease DLCO.
Clinical Aspects of Interstitial Lung Diseases (ILD)
ILD is a generic term that describes a heterogeneous group of disorders (also called diffuse parenchymal lung diseases) that are grouped together because of similar clinical, radiographic, physiologic, or pathologic manifestations. The terminology is confusing in part because of continued revisions to the classification system. ILD may result from a known cause or it may be idiopathic.
Causes of interstitial lung disease
Known causes of ILD may be grouped into one of four groups:1. Autoimmune disease 2. Exposure to inorganic dusts (typically occupational dusts such as silica or asbestos)3. Exposure to organic molecules that result in hypersensitivity pneumonitis 4. Drug effect
Idiopathic diseases
include sarcoidosis and the idiopathic interstitial pneumonias (IIPs)—this is a group of clinical diagnoses that correlate to a specific pattern of lung injury. The six major IIPs are shown below along with the pattern of injury observed (either radiographic or pathologic).
Diagnosis of interstitial lung disease
The current approach to diagnosis of ILD uses a clinical-radiologic-pathologic approach to diagnosis. Clinical information from the history and physical looks for evidence of a known cause of interstitial lung disease (autoimmune disease, exposures to drugs, organic or inorganic dusts). A radiographic pattern of disease is described by the radiologist. A pathologic pattern of lung involvement may be needed from a lung biopsy. These three streams of information are combined to come up with the best unifying clinical- radiologic-pathologic diagnosis. A specific diagnosis is important because of differences in prognosis and treatment response.
Presentation of ILD
The presentation of most forms of ILD is the insidious onset of dyspnea on exertion. Nonproductive cough is common. Rarely, the disease may be sudden in onset (examples include acute hypersensitivity pneumonitis, acute interstitial pneumonitis, acute eosinophilic pneumonia). PFTs typically show a restrictive pattern with reduced diffusing capacity.
Therapy of ILD
Therapy for many forms of ILD involves immunosuppression, although there is wide variability in response to therapy. Removal of inciting drugs or exposures is important.
Idiopathic pulmonary fibrosis (IPF)
has no response to anti-inflammatory therapy and seems be a disease of disordered alveolar epithelial repair. Two drugs were recently approved to slow the progression of IPF: nintedanib and pirfenidone.
Pulmonary fibrosis
is a generic term that refers to lung scarring. Many other forms of ILD have pulmonary fibrosis besides just IPF. Other forms of pulmonary fibrosis generally have a better prognosis than IPF.
Sarcoidosis
Sarcoid is a systemic granulomatous disease of unknown etiology that is characterized pathologically by noncaseating granulomas. Sarcoid can affect people of all racial and ethnic groups and can occur at all ages. It most frequently presents in young patients (between age 10-40 in 70-90% of cases) and usually has some degree of lung involvement. Racial/ethnic groups with increased risk include those of Scandinavian and Irish descent; African Americans have a three-fold increase risk of disease compared to Caucasian Americans; furthermore, they tend to have more severe disease and more extrapulmonary manifestations.
Granulomas
are compact collections of macrophages and epithelioid cells surrounded by lymphocytes. Macrophages combing to form multinucleated giant cells. CD4+ T cells interact with antigen-presenting cells to form and maintain granulomas. Granulomas may persist, resolve, or contribute to the development of fibrosis.
Pulmonary findings with sarcoidosis
The most frequent pulmonary finding is mediastinal and bilateral hilar lymphadenopathy (LAD). This is generally asymptomatic. Interstitial infiltrates and nodules may develop. Patients may develop pulmonary fibrosis
Symptoms of sarcoidosis
Constitutional symptoms (fevers, chills, fatigue) are common. Respiratory symptoms include dyspnea, wheezing, cough, and chest pain.
Extrapulmonary findings with sarcoidosis
Derm: Many different types: erythema nodosum (panniculitis); maculopapular rash; waxy nodules; hyperpigmented plaques especially on the face (lupus pernio). Ophthalmologic: anterior or posterior uveitis; vasculitis; keratoconjunctivitis; periorbital masses. Cardiac: related to infiltration of myocardium and/or conduction system. May result in arrhythmia or complete heart block; sudden death; heart failure. Pulmonary hypertension: this may be due to pulmonary fibrosis or due to pulmonary vascular granulomatous inflammation. Neurologic: May include granulomatous meningitis which may result in hypothalamic or pituitary involvement, or cranial nerve palsies; peripheral nerve involvement may be a late finding. Reticuloendothelial involvement: peripheral lymphadenopathy; hepatitis; splenomegaly. Metabolic: hypercalcemia occurs in up to 50% of patients due to calcitriol (1,25- dihydroxyvitamin D2) production in granulomas.
Radiographic stages of Sarcoid
Stage 1: Bilateral hilar LAD without infiltration Stage 2: Bilateral hilar LAD with infiltration. Stage 3: Infiltration without LAD Stage 4: Fibrotic disease
Lofgren’s syndrome
- Inflammatory arthritis 2. Erythema nodosum 3. Bilateral hilar lymphadenopathy. Lofgren’s syndrome often has constitutional symptoms without respiratory symptoms. It is usually self-limited and does not require treatment in most cases.
Diagnosis of Lofgren’s syndrome
Diagnosis relies on compatible clinical findings and the finding of well-formed granulomas in involved tissue. Other causes of granulomas must be excluded—especially infection. Affected tissue should be biopsied. For the lung, bronchoscopy with transbronchial biopsy is usually diagnostic; mediastinoscopy to excise a lymph node is frequently performed if the bronchoscopy is nondiagnostic. A surgical lung biopsy is occasionally required. The angiotensin-converting enzyme test may be elevated, but is not useful due to its low sensitivity and specificity. Bronchioloalveolar lavage shows a lymphocyte predominance. PFTs are usually normal in patients with stage 1 disease. More than half of all patients with sarcoid have evidence of airflow limitation with reduced FEV/FVC ratio; they may have a bronchodilator response. Patients with infiltrative disease have a restrictive pattern with reduced diffusing capacity (DLCO). Mixed obstructive and restrictive disease is relatively common.
Treatment of Lofgren’s syndrome
Most patients do not require therapy for sarcoidosis. Progressive organ involvement is treated with corticosteroids or other cytotoxic drugs (e.g. methotrexate). PFTs should be regularly followed to assess the course of disease and to guide therapy.
Differential diagnosis of granulomatous lung disease
Infection (esp Mycobacterial (TB) and fungi), Sarcoid, Hypersensitivity pneumonitis, Hot tub lung, Granulomatosis with polyangiitis, Aspiration, Talc granulomatosis, Chronic beryllium disease, Common variable immunodeficiency (CVID)
Chronology of the TB pathogenesis
stage 1: ingestion by resident alveolar macrophages. Then the cell can either kill MTB through phagosome-lysosome fusion or apoptotic death of macrophages. But if the MTB multiplies and leads to necrotic death of macrophages than the MTB survives and are released extracellularly and are taken up by other macrophages. Stage 2: symbiotic stage- MTB multiplies and macrophages accumulate. Blood monocytes migrate into the lung and differentiate into macrophages. Continued ingestion but no destruction of MTB occurs. MTB multiplies within inactivated macrophages. Formation of early primary tubercle occurs. Stage 3: migration of t cell to site of infection. T-cells begin to activate macrophages to kill or prevent spread of MTB. Granulomas form (MTB is unable to multiply within the solid caseous material). In AIDS patients, CD4+ lymphopenia results in granuloma breakdown, resulting in the inability to control the primary infection or in reactivation of latent infection. The Granuloma contains infection. Stage 4a: latent tuberculosis infection at a cellular level. Solid caseous center remains intact. Any bugs that escape the caseous edge are ingested by highly activated macrophages. LTBI is established if the caseation remains solid and does not liquefy. Stage 4b: decline in immunity leads to reactivation of TB. Immunosuppression due to AIDS, cancer, anti-TBF alpha, aging, malnutrition, etc. This leads to loss of intergrity of granuloma and liquefaction of caseous material (caseous necrosis), which provides a favorable medium for multiplication of MTB. Cavity forms and ruptures and spread to other parts of the lung and to other individuals.
Ghon complex
a lesion seen in the lung that is caused by tuberculosis. The lesions consist of a calcified focus of infection and an associated lymph node. These lesions are particularly common in children and can retain viable bacteria, so are sources of long-term infection and may be involved in reactivation of the disease in later life.
Ranke complex
is seen in ‘healed’ primary pulmonary tuberculosis comprised of two parts: Ghon lesion: calcified parenchymal tuberculoma and ipsilateral calcified hilar node
Interferon-γ release assays (IGRA)
are medical tests used in the diagnosis of some infectious diseases, especially tuberculosis. Interferon-γ (IFN-γ) release assays rely on the fact that T-lymphocytes will release IFN-γ when exposed to specific antigens. These tests are mostly developed for the field of tuberculosis diagnosis, but in theory, may be used in the diagnosis of other diseases which rely on cell-mediated immunity, e.g. cytomegalovirus and leishmaniasis. For example, in patients with cutaneous adverse drug reactions, challenge of peripheral blood lymphocytes with the drug causing the reaction produced a positive test result for half of the drugs tested.
Tram-tracks
or the tram-track sign, are medical signs that bear some resemblance to tramway tracks. When found in the lungs, tram-tracks are radiologic signs that are usually accompanied by pulmonary edema in cases of congestive heart failure and bronchiectasis. Tram-tracks are caused by bronchial wall thickening, and can be detected on a lateral chest X-ray.
The finger in glove sign
can be seen on either chest radiograph or CT chest and refers to the characteristic sign of a bronchocoele.In bronchial obstruction, the portion of the bronchus distal to the obstruction is dilated with the presence of mucous secretions (mucus plugging).
Lung hysteresis
is evident when observing the compliance of a lung on inspiration versus expiration. The difference in compliance (volume/pressure) is due to the additional energy required during inspiration to recruit and inflate additional alveoli. The transpulmonary pressure vs Volume curve of inhalation is different from the Pressure vs Volume curve of exhalation, the difference being described as hysteresis. Lung volume at any given pressure during inhalation is less than the lung volume at any given pressure during exhalation.
Spine sign
paradoxically increased density of lower spine seen on lateral chest x-ray indicative of a lower lobe process such as pheumonia.
Kerley B lines
These are short parallel lines at the lung periphery. These lines represent interlobular septa, which are usually less than 1 cm in length and parallel to one another at right angles to the pleura. They are located peripherally in contact with the pleura, but are generally absent along fissural surfaces. They may be seen in any zone but are most frequently observed at the lung bases at the costophrenic angles on the PA radiograph, and in the substernal region on lateral radiographs. Causes of Kerley B lines include; pulmonary edema, lymphangitis carcinomatosa and malignant lymphoma, viral and mycoplasmal pneumonia, interstital pulmonary fibrosis, pneumoconiosis, sarcoidosis. They can be an evanescent sign on the CXR of a patient in and out of heart failure.
Two types of reasoning in differential diagnosis
Two types of reasoning are used: (1) mental short cuts called heuristics and (2) analytical reasoning. Heuristics use pattern recognition and rely on previous experience to reach a diagnosis. They are quick, but predisposed to various biases that may result in error. Analytic reasoning is a more systematic approach that is more time- consuming, but may result in less error. Physicians employ both of these strategies in their clinical reasoning. A useful process is to consider which data elements support a suspected diagnosis and which argue against it.
What is amyotrophic lateral sclerosis?
Amyotrophic lateral sclerosis (aka Lou Gehrig’s disease) is a relentlessly progressive neurodegenerative disease that causes weakness. Progressive muscle weakness causes upper and lower motor neuron dysfunction. Patients may develop dysphagia due to uncoordinated pharyngeal muscle movement resulting in aspiration of fluids and food. Rare (1-3 cases/100,000 incidence). No racial or ethnic predilection. May occur in 3rd decade, incidence peaks in 7th or 8th
Pulmonary Manifestations of ALS
Chronic aspiration due to uncoordinated pharyngeal muscle movement (“bulbar dysfunction”). Recurrent pneumonia. Respiratory muscle weakness: Inadequate ventilation, Nocturnal hypoventilation, Weak cough. PFTs with neuromuscular diseases
Restrictive pattern
reduced FEV1, FVC; normal ratio; reduced TLC. Reduced FVC in supine position. Reduced maximal inspiratory pressure (MIP) and reduced maximal expiratory pressure (MEP). Reduced maximum voluntary ventilation. Generally normal DLCO initially; prolonged hypoventilation results in atelectasis and shunt. Elevated PCO2 or hypercarbia in arterial blood gas
Treatment of lung involvement with neuromuscular disease
noninvasive positive pressure ventilation. Aspiration precautions. Cough assistance.
Other neuromuscular disease that can affect the lung
guillain- barre syndrome can affect lungs acutely. Multiple sclerosis (MS) has a relapsing affect on the lungs. ALS is chronic and progressive. MS, infarct, trauma, tetanus, transverse myelitis, and tumors can affect the spinal cord. ALS, poliom GBS, phrenic nerve injury can affect motor nerves. Botulism, MG, lambert eaton, organophosphates can affect neuromuscular junctions. Hypokalemia, hypophos, muscular dystrophy, polymyositis, thyroid disease can affect the muscles,
Rheumatoid Arthritis (RA)
is an autoimmune disease with a hallmark of symmetric, inflammatory arthritis. Relatively common: incidence is 40/100,000. Prevalence of 1% in Caucasians. 2-3 times more common in women. Inflammatory arthritis is distinguished from mechanical arthritis (osteoarthritis) by prolonged morning stiffness. The exam may demonstrate synovitis with tender, swollen, boggy joints. The distribution in RA is usually symmetric small (MCP/PIP/MTP) and large joints (wrists, shoulders). Labs show a positive rheumatoid factor and an anti- cyclic citrullinated peptide (a more specific test). Treated with anti-inflammatory drugs and disease modifying immunosuppressive drugs.
Pulmonary Manifestations of Rheumatoid Arthritis
Pleuritis. Pleural Effusion. Pleural Thickening. Pneumothorax. Upper airway obstruction (cricoarytenoid arthritis). Small airway obstruction (bronchiolitis, bronchiectasis). Interstitial Lung Disease (UIP > NSIP). Organizing pneumonia. Nodules. Pulmonary Hypertension. Vasculitis. Drug reactions (esp methotrexate, sulfasalazine). Pulmonary infections due to immunosuppression
Pleural fluid in RA
culture is negative and cytology is negative. Total protein 4 g/dL (ratio 0.6). LDH 1100 IU/L (ratio (1.8). Glucose 12 mg/dL. pH 7.05. WBC 3000/mm3 (60% lymphs)
Connective tissue diseases with prominent pulmonary manifestations
Systemic lupus erythematosus. Rheumatoid arthritis • Systemic sclerosis (scleroderma). Sjogren’s disease. Dermatomyositis/polymyositis. Mixed connective tissue disease. Ankylosing spondylitis
Differential for hemoptysis
Alveolar hemorrhage syndrome includes Pulmonary capillaritis (Vasculitis, Connective tissue disease, Drugs), Bland hemorrhage (CTD, Anticoagulants, and Mitral stenosis), Diffuse alveolar damage (Infection leading to ARDS, Viral pneumonia, Drugs). Localized infection includes Pneumonia, abscess. Airways problems include Bronchitis, Bronchiectasis, Cancer, Foreign body. Vascular disease includes Pulmonary embolism and Pulmonary AVM, Elevated PCWP (Mitral stenosis and LHF).
Differential for acute kidney injury
Pre-renal: poor perfusion due to Hypovolemia or Decompensated HF, cirrhosis. Intrinsic issues can involve Vascular, Glomerular, or Tubular/Interstitial issues. Post renal/obstructive. Vascular problems may include Microangiopathy and hemolytic anemia, Renal infarction, Renal vein thrombosis. Glomerular problems may include Nephrotic pattern or Nephritic pattern. Tubular/Interstitial problems may include Acute tubular necrosis, Acute interstitial nephritis, Tumor lysis syndrome.
Systemic diseases associated with diffuse alveolar hemorrhage and renal disease
Granulomatosis with polyangiitis (formerly Wegener’s). Microscopic polyangiitis. Churg-Strauss Syndrome. Goodpasture’s Syndrome (Anti-GBM disease). Systemic Lupus Erythematosus. Systemic Sclerosis (Scleroderma). Henoch-Schonlein Purpura. Cryoglobulinemia
Goodpasture’s Syndrome
Goodpasture’s syndrome is an idiopathic disease that manifests as diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis. The disease is thought to be mediated by antibodies directed against glomerular basement membrane
Pulmonary Manifestations of Inflammatory Bowel Disease
Tracheobronchitis. Subglottic stenosis. Bronchiectasis. Bronchiolitis. Pleural Effusion. Interstitial Lung Disease. Pulmonary embolism. Drug complications. Infections
Sickle Cell Disease
Abnormal hemoglobin S forms polymers in RBCs that distort normal shape of cells when HbS deoxygenated. Results in occlusion of capillaries with subsequent tissue injury and pain; vaso-occlusive crises. Distorted RBCs are removed from circulation. Spleen autoinfarcts. Autosomal recessive due to single codon mutation. HbS protective against malaria.
Pulmonary Manifestations of Sickle Cell Disease
Infection. Embolic phenomena due to bone marrow infarction and fat emboli. Infarction caused by in-situ thrombosis. Hypoventilation due to rib and sternal infarctions. Pulmonary Edema due to excessive hydration. Pulmonary hypertension. Chronic lung disease
The acute chest syndrome
is a vaso-occlusive crisis of the pulmonary vasculature commonly seen in patients with sickle cell anemia. This condition commonly manifests with pulmonary infiltrate on a chest x-ray. The crisis is a common complication in sickle-cell patients and can be associated with one or more symptoms including fever, cough, excruciating pain, sputum production, shortness of breath, or low oxygen levels. Broad spectrum antibiotics to cover common infections like strep pneumoniae and mycoplasma, pain control, and blood transfusion. Acute chest syndrome is an indication for exchange transfusion.
Pulmonary complications in HIV
infections include bacterial pneumonia, tuberculosis, pneumocystis jirovecii (PCP), fungal pneumonia, and viral pneumonia. Noninfectious issues include kaposi’s sarcoma, non-hodgkin’s lymphoma, lung cancer, emphysema, ILD: LIP, org, pna, NSIP, pulmonary HTN, and effusions (parapneumonic, TB, and malignant—especially lymphoma). CD4 count is indicative of immunosuppression.
Asthma
a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing particularly at night or in the early morning. These episodes are usually associated either with widespread, but variable airflow obstruction with in the lung that is often reversible spontaneously or with treatment.
Asthma
has classically been divided into two basic types - intrinsic and extrinsic. Extrinsic asthma is initiated by a type I hypersensitivity reaction induced by exposure to an outside agent. Subtypes include atopic or allergic asthma, occupational asthma, and allergic bronchopulmonary aspergillosis. Intrinsic asthma is initiated by diverse, non- immune mechanisms, including ingestion of aspirin, infection (viral), cold, inhaled irritants, stress, and/or exercise. In patient care, these divisions are not that meaningful as patients overlap categories.
Factors that influence the development of asthma
Host factors including a genetic predisposition to atopy or airway hyperresponsiveness, obesity, and sex. Environmental factors such as exposure to allergens (dogs, cats, mice, cockroach allergen, fungi, mold, pollen), infection (viral), occupational exposures (isocyanates), tobacco smoke, air pollution, and diet.
Airway Inflammation in Asthma
the airway inflammation in asthma is persistent even though symptoms may be intermittent. The inflammation affects all airways but its physiologic effects are most pronounced in the medium sized bronchi. The following are inflammatory cells involved in asthmatic airways: mast cells, eosinophils, T lymphocytes (Th2), dendritic cells, macrophages and neutrophils.
Mast cells involvement in asthma
activated mucosal mast cells release bronchoconstrictive mediators including histamine, leukotrienes, and prostaglandin D2. Mast cells are activated by allergen via IgE receptors.
Eosinophils involvement in asthma
found in large numbers in the airways. Can release proteins that
damage epithelial cells
T lymphocytes (Th2) involvement in asthma
found in large numbers in the airways and release
cytokines including IL-4, IL-5, IL-9 and IL-13 causing IgE production by B-
lymphocytes.
Dendritic cells involvement in asthma
sample allergens
Macrophage involvement in asthma
can be activated by allergens and release inflammatory cytokines
Neutrophils involvement in asthma
increased in airways and sputum in patients with severe asthma.
Structural airway changes in asthma
Increase in airway smooth muscle cells due to hypertrophy and hyperplasia. Blood vessel proliferation. Mucus hyper-secretion in the context of increased number of goblet cells and
increase size of submucosal glands.
Airway narrowing is the final common pathway to symptoms and physiologic change in asthma and is due to airway smooth muscle contraction, airway edema, airway thickening or remodeling, and mucus hyper-secretion or plugging.
Increased tone of bronchial smooth muscle in asthma
Most agents that exert an effect on airway smooth muscle (ASM) act through specific surface receptors. A contractile substance (agonist) such as acetylcholine or histamine binds to a specific receptor to initiate a cascade of biochemical events that ultimately leads to an increase in smooth muscle contraction. The agonist’s effects may be negated by blocking the receptor with an antagonist (e.g. anti-cholinergic or anti-histamine).
Neural regulation of the airway diameter
a) Cholinergic (parasympathetic) motor neurons innervate the airways via the vagus nerve, synapsing near airway smooth muscle. The parasympathetic system provides the most important neural mechanism of bronchoconstriction. These neurons release the neurotransmitter, acetylcholine (ACH), which is a potent stimulator of ASM contraction. b) Sympathetic neurons seem to have little direct effect in determining airway caliber. c) Neurogenic inflammation refers to the inflammatory responses caused by tachykinins that activate specific receptors as part of the Nonadrenergic noncholinergic (NANC). Excitatory NANC (eNANC) effects are mediated by release of tachykinins such as neurokinin A and substance P acting on NK1 and NK2 receptors. NK1 mediate gland secretion, vasodilation, and leukocyte adhesion. NK2 mediates contraction of airway smooth muscle. Inhibitory NANC (iNANC) are thought to be mediated by vasoactive intestinal peptide and nitric oxide.
Beta-Adrenergic system regulation of the airway diameter
This is an important regulatory pathway in ASM. Beta-adrenergic agents such as isoproterenol or metaproterenol increase intracellular cAMP by activating G proteins. Beta-adrenergic agents cause ASM relaxation and are a cornerstone of the treatment of reactive airway disease.
Ion Channels regulation of the airway diameter
Primarily calcium and potassium channels. Inhaled anesthetics can have some effects on these channels, but ion channel blockers and activators are not a key part of treating asthma.
Physiologic Consequences of Airflow obstruction
During an asthma attack there is increased resistance to airflow, which is accentuated in expiration, causing air trapping and an increase in FRC and other lung volumesà hyperinflation. Hyperinflation, noted on the chest radiograph as flattening of the diaphragm, results in an increase in the work of breathing. Muscle fibers of the flattened (shortened) diaphragm cannot generate adequate tension and are operating at a suboptimal point on their length-tension curve. Remember that as the diaphragm flattens the radius of curvature increases, so based on LaPlace’s law, less pressure is generated for each corresponding increment of tension. Therefore, hyperinflation decreases tension generated and decreases pressure for that tension. Hence, in addition to overcoming increased airway resistance, the asthmatic must use less efficient respiratory muscles to inflate their lungs. Furthermore, these pathophysiologic effects increase oxygen consumption and carbon dioxide production by the diaphragm (and other respiratory muscles).
Interview questions for asthma patients
Have you ever been intubated for an asthma exacerbation? In the past six /twelve months, have you been in the hospital or
the emergency room? Are you now or have you been on oral corticosteroids for your
asthma? Have you had an increase in use of your inhalers in the past
day/week? Do you frequently awake at night because of your asthma?
Alterations in spirometry and lung volumes in asthma
In patients experiencing an exacerbation of their disease, PFT’s show an obstructive pattern. Between attacks, patients often have normal or near normal pulmonary function, although their airways remain hyperreactive (sensitive to cold air, allergens, smoke, perfume, pollutants, exercise, etc.). During an asthma attack airway obstruction leads to a decrease in FEV1/FVC. Usually this can be reversed (or improved) with a beta-adrenergic agent. An improvement of FEV1 or FVC of greater than 12% (and an absolute increase of > 200mL) is considered a positive bronchodilator response and is evidence of reversibility. Because of the air trapping, TLC, RV and FRC are increased as well and may be reversed with treatment. Peak expiratory flows (PEF; measured in liters per minute and compared to expected values) are used as an easy measurement of airflow limitation. They can be measured by patients at home.
Natural History of Asthma
The clinical course is variable. Childhood asthma patients experience complete remission more frequently than adults do. Progression to severe disease is rare in all age groups. In many asthmatics, the clinical course of the disease is characterized by exacerbations followed by complete remissions. Under treatment may result in structural changes with airway narrowing that may become irreversible: airway remodeling, and the airflow limitation similarly fixed with a progressive decline in FEV1 over time. Treatment may also change over time.
Bronchoprovocation
Useful in patients in whom the diagnosis of asthma is suspected but not definitely established. The patient performs serial spirometry after inhaling progressively higher concentrations of nebulized methacholine (or histamine) which stimulate airway obstruction in both healthy and asthmatic subjects. In asthmatics the concentration required to lower airflow (FEV1) by 20% (PC20) is several orders of magnitude lower than in healthy subjects without hyperresponsive airways. Therefore measurement of the PC20 can help diagnose asthma in patients with normal PFT’s. Bronchoprovocation can also be tested in response to exercise. Spirometry is performed, then then the patient vigorously exercises and then serial spirometry is performed after exercise to look for the development of airflow limitation.
General Triggers of Asthma
The presentation of asthma can
range from cough variant asthma, to mild exercise induced asthma to chronic respiratory disease and finally acute respiratory arrest. Asthmatics exacerbate following many different stimuli (including exercise, cold, viral infection, house mites, dust, chemicals, air pollution, etc.) but many exacerbations cannot be traced to a specific event. Coexisting conditions such as allergic rhinitis, sinusitis, postnasal drip, and gastroesophageal reflux can exacerbate asthma and should be searched for in patients with refractory symptoms. A personal or family history of atopic disease (atopic dermatitis, allergic rhinitis) is common in many patients. Obesity is a likely risk factor.
Therapy of Asthma
The emphasis of treatment is to control airway inflammation–primarily with inhaled steroids. Reducing increased airway tone also provides symptomatic benefit.
Reduce airway tone for treatment of asthma
beta-agonists (short-acting: albuterol; long-acting: salmeterol, formoterol) to stimulate beta receptors and cause ASM relaxation. anti-cholinergics (ipratoprium, tiotropium) to reduce ACH mediated ASM
contraction. leukotriene inhibitors (montelukast; zileuton) to reduce the vasoconstricting
effects of leukotriene which are released by activated mast cells. methylxanthines (theophylline) are phosphodiesterase inhibitors that increase
intracellular cAMP concentrations
Reduce inflammation for treatment of asthma
corticosteroids: oral, inhaled, or intravenous are effective and are thought to act
by 3 mechanisms (not acute):
1. reducing the number of inflammatory cells (eosinophils, neutrophils,
lymphocytes)
2. inhibiting the release of leukotrienes and prostaglandins by effector
cells.
3. decreasing airway edema. mast cell stabilizers (cromolyn; nedocromil inhibit the release of pro-inflammatory agents. leukotriene inhibitors (montelukast; zileuton) reduce number of inflammatory cells (particularly eosinophils) and reduce vasoconstricting effects of leukotrienes released from activated mast cells. Anti-Ig E therapy (omalizumab) decreases IgE binding to basophils and mast cells in patients with allergies and severe asthma
Chronic treatments choices for asthma
are determined based on the severity of asthma. If asthma is not controlled, step-up therapy should be used; if asthma is well controlled, a trial of step-down therapy may be appropriate.
Treatment of acute asthma exacerbations
Acute exacerbations are treated with systemic corticosteroids to decrease inflammation. Inhaled bronchodilators (SABA, anticholinergics) are used to treat acute symptoms. Supportive care for severe cases may include noninvasive positive pressure ventilation or, rarely, invasive mechanical ventilation.
Churg–Strauss syndrome
(CSS, also known as eosinophilic granulomatosis with polyangiitis [EGPA] or allergic granulomatosis) is an autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy).
Intermittent asthma
symptoms less than twice per week and asymptomatic between episodes. Nighttime awakenings less than twice per month. Treatment is SABA PRN.
Mild persistent asthma
symptoms between than twice per week and once daily. Nighttime awakenings greater than twice per month.
Moderate persistent asthma
daily symptoms, multiple exacerbations per week. Nighttime awakenings more than once per week.
Severe persistent asthma
continual symptoms, constant limitations of activity, frequent exacerbations and nightly awakenings.
Chronic obstructive pulmonary disease (COPD)
COPD is a common disease defined by irreversible airflow limitation (FEV/FVC
