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.