The trachea and bronchi are made of a rich epithelial cell surface composed of ciliated cells, secretory goblet cells, subepithelial cells (containing cartilage for structural support of the airways), and inflammatory mediator cells and glands. The amount of cartilage decreases as the respiratory tree branches distally and disappears altogether in the small airways (<2 mm in diameter). Tracheobronchial glands, which secrete mucus, are bigger and more numerous in the proximal airways.

Cells dedicated to airway defense are found scattered within the epithelium and submucosa. Lymphocytes may appear singly or in clusters, especially at branching points or airway bifurcations, and are called bronchus-associated lymphoid tissue. Plasma cells, especially IgA, mast cells, and macrophages, are also found at airway bifurcations. Mast cells increase in the transition zone leading to the distal airway, where gas conduction occurs. Marked branching of the airways continues as surface area is maximized for gas exchange. This architecture helps to keep the area below the main carina sterile.

The lower respiratory tract is uniquely equipped to protect against invading organisms. Aspiration of upper airway flora is the most important risk for infection. Defense mechanisms include a good cough reflex, effective mucociliary clearance (continual upward beating of cilia) to remove bacteria and debris, and angulation of airways, which traps and impinges bacteria at bifurcations. For infection to occur, the following sequential steps are required, especially at oropharyngeal colonization; aspiration of organisms; bacterial attachment to epithelial cell surfaces, preventing normal epithelial cell desquamation; and subsequent removal by expectoration.

The risk of lower airway infection is further increased by both the type of oral microflora present in the airways and host susceptibility. Severely ill patients lose their normal flora and become increasingly susceptible to enteric gram-negative bacilli. Clearance mechanisms progressively malfunction and are associated with abnormalities in mucosal surfaces. A recent viral infection may effectively strip the normal mucosa, causing intense cellular desquamation and loss of mucociliary function and local phagocytic function.

Within the terminal airway, the alveolar macrophage is the primary cellular defense. Alveolar macrophages are capable of overwhelming a challenge of low virulence—for instance, a normal, nocturnal, small-volume aspiration of oropharyngeal secretions. Activated alveolar macrophages also are capable of activating the immune system by recruiting polymorphonuclear leukocytes, found in pulmonary microvasculature reserves.

In addition, alveolar macrophages secrete cytokines, which trigger the intercellular communication systems of the immunologic response. Important lung cytokines include tumor necrosis factor, interleukin 1, and interleukin 8. They are produced in response to alveolar macrophages that activate mononuclear cells to release gamma colony stimulating factor (G-CSF). G-CSF increases myeloid progenitor cells, which trigger polymorphonuclear leukocytes to promote adhesion, chemotaxis, phagocytosis, and phosphorylation at local sites to combat infection.

Pneumonia ranks as the sixth leading cause of death in the United States and is the leading cause of death attributable to an infectious disease. Current estimates for the United States are 4 million cases annually, with a morbidity rate of 12 per 1000 adults per year. Hospitalizations approach 600,000 per year, at an annual cost of $23 billion (MMWR, 1995a, b).

All humans are susceptible to lower respiratory tract infections. Symptoms of acute bronchitis in a previously healthy person implicate common cold viruses: rhinovirus, respiratory syncytial virus, parainfluenza, coronavirus, or adenovirus. Influenza
A or B may also be a cause. Nonviral agents include Mycoplasma pneumoniae, Chlamydia pneumoniae (originally described as TWAR), and Bordetella pertussis, an increasingly common pathogen in susceptible adults with persistent cough.

Patients with comorbid medical problems, underlying cardiorespiratory illness, immunocompromised status, or impaired cough reflex are at higher risk for infection with the usual respiratory flora and pathogenic bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and Legionella.

Chronic bronchitis is more common in tobacco users and those exposed to passive smoke. Inhaled irritants in tobacco smoke may decrease ciliary mucosal transport and decrease the phagocytic function of the pulmonary immunologic response. These increase the risk for both colonization and infection, especially by S. pneumoniae, H. influenzae, and M. catarrhalis.

Primary bronchiectasis is associated with multiple insults to the lung and is divided into the following main categories:

Secondary bronchiectasis is associated with inherited or congenital diseases. Cystic fibrosis is the most common; others include immunoglobulin deficiencies and ciliary dyskinetic syndromes.

Predisposing epidemiologic factors leading to lung abscess include events related to impaired consciousness or sensorium, as well as esophageal motility disorders, history of seizures, or the use of alcohol or illicit drugs. These become even more significant in the presence of poor oral hygiene or gingivitis. Anaerobes account for 80% to 90% of all pulmonary suppurative lung abscesses. This is not surprising, given that inflamed gingival surfaces and crevices harbor a large volume of anaerobes (as high as 10¹² organisms/g).

Evaluation of the epidemiologic setting and the physical exam can yield clues suggesting the most likely pathogen causing pneumonia (Tables 75-1 and 75-2).

The diagnosis of both acute and chronic bronchis is based on a constellation of clinical symptoms and findings.

Patients with bronchiectasis present with a prolonged history of recurrent sinopulmonary infections and chronic cough productive of copious amounts of purulent sputum intermittently streaked with blood. The chest radiograph shows hyperlucent cystic areas and peribronchial fibrosis demonstrated by “tram tracks,” clearly delineated vertical or parallel lines of a descending bronchus. Thin-section chest computed tomography confirms the diagnosis. When contrast is administered, the so-called “signet ring” sign is seen, showing the diameter of the involved bronchus larger than its accompanying pulmonary artery.

The chest film in lung abscess reveals single or multiple thick-walled cavitary lesions with air-fluid levels. These lesions are generally located at dependent areas of the lungs, especially the superior segments of the lower lobes. Microbiologic diagnosis can be made by Gram stain and culture of sputum specimens.

The clinical spectrum in pneumonia varies, depending on whether the infection is community-acquired. Typical pneumonia presents with fever, productive cough, pleuritic chest pain, and clinical signs of consolidation. In atypical pneumonia, systemic symptoms predominate (eg, fever, headache, myalgias, dry or minimally productive cough, and lack of clinical signs of consolidation).

The chest radiograph demonstrating an infiltrate is the gold standard for the diagnosis of pneumonia. Radiographic abnormalities cannot distinguish bacterial from atypical pneumonia. Chest films can, however, help assess the extent and severity of illness; evaluate complications such as atelectasis, pleural effusion, or multilobar involvement; and assist in planning further diagnostic studies. Difficulties may arise in the interpretation of pneumonia in the presence of coexistent lung diseases or congestive heart failure, as well as in patients who cannot participate in taking standard posteroanterior/lateral films. Suboptimal films must be evaluated within the context of both the clinical presentation and findings. A repeat chest x-ray for diagnostic accuracy may be necessary once the patient can fully participate.

The etiologic diagnosis of pneumonia is based on microbiologic criteria. A definitive diagnosis is made when a pathogenic organism is recovered from a normally sterile site, i.e. blood or pleural fluid, or when an organism that is not a known colonizer is found in respiratory secretions, for example: viral organisms Influenza A or B; respiratory syncytial virus (RSV); herpesvirus (HSV); cytomegalovirus (CMV); Pneumocystis carinii Pneumonia (PCP); any fungi; Legionella; Mycoplasma pneumoniae; Chlamydia pneumoniae (TWAR); Bordetella pertussis; acid fast bacilli: Mycobacterium tuberculosis (MYB) or any atypical pathogenic acid fast bacillus.

Sputum Gram stains are an important diagnostic tool, provided that they are collected appropriately. The specimen must be collected before the initiation of antimicrobial therapy and must contain greater than 25 polymorphonuclear leukocytes and less than 10 epithelial cells per high-power field, demonstrating a true distal airway specimen not contaminated by saliva.

Failure to detect gram-positive clusters or gram-negative bacilli in the initial specimen virtually excludes these organisms from diagnostic consideration. In addition, the Gram stain may allow the detection of penicillin-resistant strains of S. pneumoniae. The inability to identify a predominant organism on Gram stain despite the presence of 25 polymorphonuclear leukocytes and less than 10 epithelial cells suggests the possibility of atypical pathogens, such as Legionella, Mycoplasma, Chlamydia, or a viral etiology or the use of antimicrobial therapy before obtaining the sputum for diagnostic studies.

In acute bronchitis, a complete history should be taken, with careful attention to epidemiologic considerations (eg, occupation, recent community outbreak of influenza, overcrowded living conditions, a history of concurrent infections of close contacts). A thorough physical exam focused on the eyes, ears, nose, sinuses, throat, and cardiorespiratory system is crucial. Productive or nonproductive cough, together with retrosternal discomfort with or without wheezing, localizes symptoms to the lower airways. The physical exam is otherwise generally within normal limits. Fever is absent in most viral syndromes responsible for the common cold, most commonly rhinovirus, respiratory syncytial virus, or coronavirus. Fever is a component of influenza A and B, adenovirus, M. pneumoniae, C. pneumoniae, and B. pertussis infections. Lung auscultation reveals basilar rhonchi or rales that may change or clear with cough. Wheezing is also a nonspecific finding; it may persist long after other symptoms and signs have resolved.

Chronic bronchitis is present in cigarette smokers or persons exposed to chemical or environmental irritants, including passive smoke inhalation. There is a history of progressive exercise intolerance and episodic cough with increased expectoration of mucopurulent sputum. Prolonged recurrences may lead to arterial blood gas derangements, severe hypoxemia, and hypercarbia. In later stages this may lead to pulmonary artery hypertension and right-sided heart failure. The physical exam may reveal coughing and an increased respiratory rate associated with respiratory distress and abnormal breathing patterns. On auscultation, rhonchi and decreased air entry may be heard. Wheezing may be intermittent, especially if associated with acute mucus plugging of a bronchus. In later stages, if pulmonary hypertension ensues, a parasternal right ventricular heave and loud S₂ may be noted. Lower extremity edema may be present if right-sided heart failure occurs.

Bronchiectasis produces copious mucopurulent, often blood-streaked sputum of many years’ duration and recurrent sinopulmonary infections. The physical exam reveals a chronically ill-appearing patient and possibly muscle wasting, malnutrition, and failure to thrive. Clubbing of the fingers from chronic hypoxemia may occur. On auscultation, coarse rales with variations in pitch and volume at both inspiration and expiration are often heard, as well as coarse rhonchi representing secretions in large airways.

Patients with lung abscess typically present with an insidious course of a 2- to 4-week duration of fever, purulent fetid blood-streaked sputum, generalized malaise, anorexia, and weight loss. Chest pain is common. On the physical exam, low-grade fever is present. The patient appears chronically ill and pale. The oral exam reveals poor dentition or gingivitis and overall poor dental hygiene. Signs of consolidation may be heard on auscultation, accompanied by amphoric or tubular breath sounds over the site of the lung abscess. When empyema invades the pleural space, pleuritic chest pain may be prominent, and dullness to percussion is encountered.

Symptoms suggestive of pneumonia are nonspecific and include fever, cough, sputum production, shortness of breath, and chest pain. The mean duration of illness before seeking medical attention is usually 5 to 6 days. Fever occurs in approximately 80% of patients. Another 30% have signs of consolidation with egophony. Most patients have at least one of these symptoms.

Those at highest risk for complications of pneumonia are persons with comorbid illness such as chronic obstructive pulmonary disease, congestive heart failure, immunosuppression (including chronic steroid use), diabetes mellitus, renal insufficiency, chronic liver disease, postsplenectomy, or chronic alcohol or illicit drug use and malnutrition, or those older than 60 years.

The definitive laboratory diagnosis of an upper respiratory viral infection causing acute bronchitis is unnecessary. Chest x-rays should be obtained in all patients who appear ill to exclude a more serious lower respiratory infection.

Chronic bronchitis is also diagnosed primarily on symptoms. Recurrent episodes of clinical deterioration can occur, especially when complicated by upper respiratory infection and fever or increased volume or purulence of sputum. Patients may appear cyanotic and the arterial blood gas analysis may reveal hypoxemia and hypercapnea. Repeated recurrences may lead to permanent blood gas derangements and chronic ventilatory failure characterized by well-compensated respiratory acidosis. This is evidenced by elevated serum bicarbonate levels, confirming renal compensation for the chronic hypercarbia. Erythrocytosis and elevations of hemoglobin and hematocrit are seen on a routine complete blood count as evidence of the compensatory response to chronic hypoxemia. Leukocytosis may be a feature of bacterial infection. An appropriately collected and rapidly processed Gram stain of the sputum with culture will identify the primary bacterial pathogen, or a superinfection after an episode of viral, mycoplasmal, or chlamydial infection. The usual bacterial pathogens include S. pneumoniae, H. influenzae, and M. catarrhalis. Enteric gram-negative organisms, especially Klebsiella and Pseudomonas, should also be excluded. Electrocardiography may show supraventricular arrhythmias, intraventricular conduction defects, right ventricular strain, right ventricular hypertrophy, right bundle branch block, and morphologic P-wave abnormalities, all related to hypoxemia. Chest radiography is nonspecific and may suggest hyperinflation, bronchial prominence, or other signs of dilatation. If pulmonary hypertension is present, enlarged pulmonary arteries may be seen. In cor pulmonale, an enlarged right ventricle may be seen on chest films. Spirometry indicates signs of airflow obstruction with a decrease in forced expiratory volume in 1 sec (FEV₁) and in the ratio of FEV₁ to forced vital capacity.

In bronchiectasis, hypercarbia with ensuing chronic ventilatory failure is seen in late-stage disease. Additional diagnostic options are tailored to the patient. When an appropriate clinical or family history suggests cystic fibrosis as the etiology for bronchiectasis, a sweat chloride determination with pilocarpine iontophoresis should be performed. Serum protein electrophoresis and IgG subsets may be obtained to evaluate for immunologic abnormalities. If fever and recurrent wheezing are present and central bronchiectasis is found on the chest radiograph, an evaluation for allergic bronchopulmonary aspergillosis should be performed. Sputum Gram stain and culture will identify bacterial pathogens.

Bronchoscopy, percutaneous transthoracic needle aspiration, or diagnostic thoracentesis of pleural fluid have replaced transtracheal aspiration for the diagnosis of a lung abscess. In addition to examining the aspirate, blood cultures are essential. Anemia of chronic disease is usually present. When other conditions coexist, such as alcoholism or malnutrition, an iron or folate deficiency anemia may also be present. A moderate leukocytosis is often found. A computed tomography scan of the chest is often performed to evaluate the parenchyma and distinguish pleural involvement. Additional studies should be tailored to the patient and are used primarily in rapidly worsening disease.

The etiologic diagnosis of pneumonia is based on microbiologic criteria. Accurate identification of a pathogen necessitates that it be present in a normally sterile site, i.e., blood or pleural fluid, and that it not be a known colonizer in respiratory secretions. The most common pathogens for pneumonia include: any fungi, Histoplasma capsulatum, Coccidiodes immitis, Blastomyces dermatitis, Pneumocystis carinii pneumonia (PCP); parasites: Toxoplasma gondii, strongyloides; viral organisms such as Influenza A or B, respiratory syncytial virus (RSV), Herpesvirus (HSV); Legionella, Mycoplasma pneumoniae, Chlamydia pneumoniae (TWAR), and Bordetella pertussis.

In summary, all patients with an increased risk for morbidity or mortality from pneumonia require hospitalization and careful observation. Required studies include chest radiography; arterial blood gas analysis; complete blood count; chemistry profile, including electrolytes and renal and liver function tests; and microbiologic studies (blood cultures, Gram stain and culture of sputum), with additional special studies such as staining and culture for acid-fast bacilli. When Legionella is suspected, sputum for both culture and direct fluorescent antibody test (DFA), should be obtained. In addition, a urine sample for Legionella pneumonia serogroup 1 radioimmune assay is 80% to 99% sensitive and 99% specific.

Pleural fluid, if present, requires early, aggressive diagnostic thoracentesis and pleural fluid analysis with cell count and differential; pH collected anaerobically and on ice, chemistries, including: glucose, protein, and lactate dehydrogenase; Gram stain and bacterial culture; acid-fast stain; mycobacterial and fungal cultures; and cytology.