BRONCHIECTASIS, ATELECTASIS, CYSTS, AND LOCALIZED LUNG DISORDERS

Chapter 90 – BRONCHIECTASIS, ATELECTASIS, CYSTS, AND LOCALIZED LUNG DISORDERS

Alan F. Barker

   BRONCHIECTASIS

Definition

Bronchiectasis is an acquired disorder of the major bronchi and bronchioles; it is characterized by permanent abnormal dilation and destruction of bronchial walls. The affected airways show a variety of changes including transmural inflammation, mucosal edema, cratering and ulceration, bronchial arteriole neovascularization, and distortion due to scarring or obstruction from repeated infection. The obstruction often leads to postobstructive pneumonitis that may temporarily or permanently damage the lung parenchyma. The induction of bronchiectasis requires several factors: (1) an infectious insult, (2) airway obstruction, (3) reduced clearance of mucus and other material from the airways, and/or (4) a defect in host defense.

Pathobiology

Airway Obstruction

Examples of airway obstruction causing bronchiectasis include previous foreign body aspiration or encroaching lymph nodes (middle lobe syndrome). Bronchiectasis as a sequela of foreign body aspiration usually occurs in the right lung and in the lower lobes or the posterior segments of the upper lobes. It is important to identify the presence of airway obstruction (as with foreign body aspiration), because surgical resection often produces a cure. Although witnessed or recognized aspiration (Chapter 97) is uncommon, an episode of choking and coughing or unexplained wheezing or hemoptysis should raise the suspicion of a foreign body.

Particulate aspiration is typically associated with an altered state of consciousness due to stroke, seizures, inebriation, or emergent general anesthesia. The foreign body is often unchewed food or part of a tooth or crown. Delayed or ineffective therapy and poor nutrition may contribute to prolonged pneumonitis with resultant focal bronchiectasis.

Humoral Immunodeficiency

Patients with hypogammaglobulinemia (Chapter 271) usually present in childhood with repeated sinopulmonary infections. In adults, the history may include frequent episodes of “sinusitis” and “bronchitis.” Establishing the diagnosis of humoral immunodeficiency is important, because gamma globulin replacement can diminish or even prevent further respiratory tract infections and lung damage. Intravenous immunoglobulin (Ig) augmentation should be administered when levels of IgG, IgA, and IgM are less than 5 to 10% of normal values. In patients with isolated IgG subclass deficiency, tests of humoral competency, such as a serum antibody response to Haemophilus influenzae or pneumococcal antigen/vaccine, help decide whether low levels are functional.

Cystic Fibrosis

Major respiratory diseases in cystic fibrosis (CF) are sinusitis and bronchiectasis; the latter may be the sole feature of CF in adults (Chapter 89). Clues suggesting the presence of this disorder are upper lobe radiographic involvement and sputum cultures showing mucoid Pseudomonas aeruginosa or Staphylococcus aureus. An elevated sweat chloride value is diagnostic; genetic testing is warranted if the clinical findings are suggestive and sweat chloride values are borderline elevated.

Young's Syndrome

Patients with Young's syndrome exhibit clinical features similar to those observed in CF, including bronchiectasis, sinusitis, and obstructive azoospermia. They are often middle-aged men identified during evaluation for infertility. They do not have increased sweat chloride values, pancreatic insufficiency, or genetic abnormalities. No cause has been identified.

Rheumatic Diseases

Rheumatoid arthritis and Sj?gren's syndrome can be complicated by bronchiectasis (Chapters 285 and 289). Although most patients have obvious rheumatic features when the bronchiectasis is discovered, some patients have only mild arthropathy. The presence of bronchiectasis increases the mortality rate associated with respiratory infections.

Dyskinetic Cilia

Although immotile cilia were originally described in the respiratory tract and sperm of patients with Kartagener's syndrome (dextrocardia, sinusitis, bronchiectasis), other patients have dyskinetic cilia leading to poor mucociliary clearance, repeated respiratory infections, and subsequent bronchiectasis. Several candidate genes responsible for the abnormal protein involved in the modified motility of cilia have been identified.

Pulmonary Infections

Pulmonary infections have been associated with the development of bronchiectasis. Some individuals with presumed viral or Mycoplasma infection develop repeated respiratory infections and bronchiectasis. In addition to direct tissue injury, a sequela of virulent infections (tuberculosis) may result in enlarged and caseous lymph nodes around bronchi or damaged airways that predispose to bacterial colonization (Chapter 345). The recognition of bronchiectasis in acquired immunodeficiency syndrome (AIDS; Chapter 414) illustrates the accelerated destructive interaction between repeated infections and impaired host defense; highly active antiretroviral therapy may alter this cycle of repeated infection and airway damage. Childhood whooping cough (pertussis; Chapter 334) is now of mostly historical interest in the pathogenesis of bronchiectasis, and adult pertussis has not been associated with bronchiectasis. It is unclear whether many of these children had secondary bacterial pneumonia. Mycobacterium avium-intracellulare (MAI) has traditionally been considered a secondary pathogen in an abnormal host (AIDS) or in already damaged lung (bullous emphysema). However, presumed normal hosts have developed bronchiectasis with primary MAI infections (Chapter 346). The syndrome has been recognized in white women older than age 55 years with chronic cough and involvement of the middle lobe or lingula.

Allergic Bronchopulmonary Aspergillosis

Aspergillus may also be associated with bronchiectasis (Chapter 360). This disorder should be suspected in patients with a long history of asthma that is resistant to bronchodilator therapy and is associated with a cough productive of sputum plugs or mucopurulence. Allergic bronchopulmonary aspergillosis probably represents a hyperimmune reaction to the presence of the Aspergillus organism, airway damage due to mycotoxins and inflammatory mediators, and even direct infection.

Cigarette Smoking

A causal role for cigarette smoking in bronchiectasis has not been shown. However, smoking and repeated infections may worsen pulmonary function and accelerate the progression of disease that is already present.

Clinical Manifestations

Patients often report frequent bouts of “bronchitis” requiring therapy with repeated courses of antibiotics (Chapter 96). Symptoms in most patients include daily cough productive of mucopurulent phlegm, intermittent hemoptysis, pleurisy, and shortness of breath. In bronchiectasis, bleeding can be brisk; it is often associated with acute infective episodes and is produced by injury to superficial mucosal neovascular bronchial arterioles. Physical findings on chest examination include crackles, rhonchi, wheezing, or combinations of these. Digital clubbing is rare.

Diagnosis

The diagnostic evaluation is designed to confirm the diagnosis of bronchiectasis, to identify potentially treatable underlying causes, and to provide functional assessment (Table 90-1). However, a defined etiology is found in fewer than 50% of patients with bronchiectasis. Imaging of the chest is always necessary to confirm the diagnosis.

TABLE 90-1   -- BRONCHIECTASIS: DIAGNOSTIC FEATURES OF ASSOCIATED CONDITIONS

Condition	Diagnostic Test	Abnormal Result
Immunodeficiency	Quantitative IgG, IgA, IgM	All low; rarely, isolated subclass G is low
Ciliary dyskinesia	Respiratory mucosa biopsy (examine by electron microscopy)	Ciliary struts or spokes broken or missing
	Exhaled nitric oxide	Low
Bronchopulmonary aspergillosis	IgE	High, often >1000 IU/mL
	Type I and type III skin tests; precipitins	Positive
	Fungal sputum cultures	Positive about 50% of time
Mycobacterium avium-intracellulare infection	Mycobacterial sputum culture/DNA probe	Positive in about two thirds of patients
Cystic fibrosis	Sweat chloride	>55–60 mEq/L
	Sputum culture	Pseudomonas aeruginosa
	Genetic testing	ΔF508 most frequent
Foreign body aspiration	Bronchoscopy	Lobar or segmental obstruction

Ig = immunoglobulin; IU = international units.

Chest Radiography

The chest radiograph, which is abnormal in most patients with bronchiectasis, in combination with the clinical findings may be sufficient to establish the diagnosis. Suspicious but not diagnostic radiographic findings include platelike atelectasis, dilated and thickened airways (tram or parallel lines; ring shadows on cross section), and irregular peripheral opacities that may represent mucopurulent plugs. The distribution of changes also may be helpful. A central (perihilar) distribution of the abnormal shadowing is suggestive of allergic bronchopulmonary aspergillosis, whereas predominant upper lobe distribution is suggestive of CF.

High-Resolution Computed Tomography

High-resolution computed tomography (HRCT) of the chest is the defining modality for diagnosis of bronchiectasis. The major potentially progressive features of bronchiectasis on HRCT include airway dilatation, lack of airway tapering toward the periphery, bronchial wall thickening, varicose constrictions, and ballooned cysts off the end of a bronchus (Fig. 90-1). HRCT is indicated in the following settings: a patient with suspicious clinical findings but a relatively normal chest radiograph; a patient whose chest radiograph is abnormal (e.g., pneumonic infiltrate) and in whom underlying bronchiectasis is strongly suspected; a patient for whom management decisions, such as surgical resection of the abnormal areas of lung, depend on the extent of bronchiectasis; and a patient in whom the presence or absence of another confounding disease, such as chronic obstructive lung disease or interstitial lung disease, needs to be defined. The HRCT may also demonstrate other findings, such as consolidation of a segment or lobe (from pneumonia), which can be present in bronchiectasis but is not diagnostic as an isolated finding; peripheral irregular branching lines (tree-in-bud) of impacted mucus in small airways; enlarged lymph nodes, which may be indicative of reaction to infection; or areas of low attenuation and vascular disruption, probably caused by the distorting effect of inflammatory small airways and suggestive of emphysema.

FIGURE 90-1  High-resolution chest computed tomography of patients with bronchiectasis. A, Dilated airways are present in the right lung. B, In the right lung are dilated and thickened airways almost to the periphery of the lung, with a beaded appearance of varicose bronchiectasis. C, Both lungs show hugely dilated airways that cluster as cystic or saccular bronchiectasis, which is the most severe and damaging form of bronchiectasis.

Bronchoscopy

Bronchoscopy is an important diagnostic tool in focal (segmental or lobar) bronchiectasis to examine for obstruction by a foreign body, tumor, structural deformity, or extrinsic compression from lymph nodes (Fig. 90-2). Bronchoscopic lavage may help identify or confirm pathogens such as MAI, and a biopsy specimen can be examined by electron microscopy for the ultrastructural features of ciliary dyskinesia. Bronchoscopy plays a key role in patients with hemoptysis to help localize the bleeding to a lobe so that appropriate intervention can be performed.

FIGURE 90-2  Bronchoscopic photograph of endobronchial papillary tumor with complete obstruction leading to distal collapse and subsequent bronchiectasis.

Pulmonary Function Tests

Pulmonary function testing allows a functional assessment of the impairment induced by bronchiectasis. Spirometry before and after the administration of a bronchodilator is adequate in most patients. Obstructive impairment (reduced or normal forced vital capacity [FVC], low forced expiratory volume in 1 second [FEV₁], or low FEV₁/FVC ratio) is the most frequent finding, but a very low FVC is also seen in advanced disease in which much of the lung has been destroyed.

Prevention and Treatment

Antibiotics are used to treat an acute exacerbation and to prevent recurrent infection by suppression or eradication of pathogens. Acute Exacerbation The diagnosis of an acute exacerbation depends on symptomatic changes rather than any specific laboratory feature. Acute bacterial infections are usually accompanied by increased production of darker and more viscid sputum, shortness of breath, and pleuritic chest pain and are often accompanied by lassitude. Systemic complaints such as fever and chills are usually absent, and the chest radiograph rarely shows new infiltrates. Frequent bacterial pathogens include H. influenzae (Chapter 323) and P. aeruginosa (Chapter 328), often different from the pathogenic agents in patients with chronic bronchitis. Initial treatment should include a fluoroquinolone such as levofloxacin, 500 mg daily for 14 days or ciprofloxacin, 750 mg every 12 hours for 14 days. For patients who are too ill for oral therapy, parenteral therapy with two different classes of antipseudomonal agents (e.g., ceftazidime, 2 g every 8 hours plus tobramycin, 5 to 7 mg/kg/day for 14 days) is needed. The duration of therapy is not well defined, but a minimum of 7 to 14 days has become frequent practice. Sputum culture and sensitivity to help define antibiotic selection and resistance patterns are indicated in patients who have no response to the initial antibiotic or who have repeated symptomatic attacks in a short interval. Prevention Less clear is the role of suppressive antibiotic regimens. Chronic macrolide administration (e.g., azithromycin, 500 mg/day three times each week) has been shown to reduce sputum volume and coughing only for Pseudomonas. However, three organisms that contribute to symptomatic episodes and are particularly problematic and difficult to eradicate are P. aeruginosa, MAI, and Aspergillus species. P. aeruginosa (Chapter 328) is almost impossible to eradicate in patients with bronchiectasis. The quinolones, such as ciprofloxacin or a newer quinolone in doses noted earlier, are the only effective oral agents against P. aeruginosa, but resistance often develops after one to two treatment cycles. When Pseudomonas causes repeated symptomatic episodes, aerosolized tobramycin reduces the burden of Pseudomonas in the sputum and improves symptoms.[1] MAI (Chapter 346) and Aspergillus (Chapter 360) species are often harbored in damaged lung tissue and bronchiectatic airways. Guidelines to help decide whether a patient is infected with MAI or Aspergillus include (1) symptomatic episodes not responding to antibacterial agents, (2) two or more independent positive sputum cultures, (3) new infiltrates on chest radiograph with sputum culture growing either organism, and (4) HRCT showing nodular opacities with MAI infection. For the treatment of MAI infection, a three- to four-drug regimen is recommended by the American Thoracic Society, including the following: clarithromycin, 500 mg twice daily, or azithromycin, 250 mg/day; rifampin, 600 mg/day; ethambutol, 15 mg/kg/day; and streptomycin, 15 mg/kg two to three times a week for the first 8 weeks as tolerated. Therapy is continued until cultures are negative for 12 months. For patients with allergic bronchopulmonary aspergillosis, a prolonged course of prednisone (beginning at 0.5 mg/kg/day) stabilizes exacerbations. Itraconazole (400 mg/day) allows reduced steroid dosing and improves clinical outcome in some patients.[2] Bronchial Hygiene Bronchiectasis is the prototypical disease for which secretion loosening or thinning, combined with enhanced removal techniques, should be salutary. This approach is particularly important for patients in whom tenacious secretions are not reduced with appropriate antibiotic administration. Potential therapies include hydration, nebulization with saline solutions and mucolytic agents, mechanical techniques, bronchodilators, and corticosteroids. Hydration and Nebulization General hydration with oral liquids and nebulization with saline solutions or mucolytic agents are important considerations in the management of bronchiectasis. The mucolytic agent acetylcysteine is beneficial in some patients when delivered by nebulization. Although recombinant human deoxyribonuclease (rhDNase) is effective in CF, in bronchiectasis it neither reduces pulmonary exacerbations nor improves pulmonary function. Physiotherapy Mechanical techniques to loosen viscid secretions, followed by gravitational positioning, should be effective if practiced assiduously. Chest percussion techniques include hand clapping of the chest by an assistant or application of a mechanical vibrator to the chest wall. Because bronchiectasis most often follows a middle or lower lobe distribution, the patient needs to recline prone on a bed with the head over the edge for postural drainage, but this position may be difficult or uncomfortable for many patients. If physiotherapy is performed regularly, three to four times daily, enhanced sputum mobilization occurs in many patients. However, patients often do not take the time (15 to 30 minutes per session), do not have assistance to perform vibratory techniques, or cannot tolerate proper positioning to get maximal benefit. Despite decades of enthusiasm for physiotherapy, these techniques have limited value.[3] Alternatives for patients who cannot perform chest physiotherapy include handheld positive expiratory pressure devices or flutter valves, which facilitate secretion drainage by maintaining airway patency, or a vibratory vest applied to the chest. Bronchodilators Airway reactivity, presumably caused by transmural inflammation, is often present in patients with bronchiectasis. Aerosol bronchodilator therapy, as used in chronic bronchitis (Chapter 88), may be appropriate but has not been studied in patients with bronchiectasis. Anti-inflammatory Medication Because inflammation plays a major role in bronchiectasis, corticosteroid therapy might theoretically be beneficial. However, systemic steroids can further depress host immunity and promote increased bacterial and fungal colonization and even perpetuation of infection. One practical approach involves oral systemic prednisone therapy (20 to 30 mg/day for 2 days, tapering completely over 10 to 14 days) along with antibacterial therapy at the time of acute exacerbations. Regular inhaled steroids could be considered at other times. In pilot studies of aerosolized beclomethasone (2 puffs of 80 μg each, twice daily), and fluticasone (2 puffs of 220 μg each, twice daily), treated patients had fewer inflammatory mediators in their sputum, less sputum production, reduced coughing, and improved pulmonary function.[4] Hemoptysis Bleeding in bronchiectasis can be brisk and life-threatening. It is often associated with acute infective episodes and is produced by injury to superficial mucosal neovascular bronchial arterioles. HRCT and bronchoscopy may help localize the bleeding to a lobe or segment. Selective bronchial arterial embolization, when available, is the treatment of choice, because it preserves lung tissue. Thoracotomy and resection (Chapter 102) may still be necessary if bleeding persists. Surgery The combination of impaired defense mechanisms and recurrent infection often results in bronchiectasis' becoming a diffuse lung disease with little opportunity for surgical cure. Nevertheless, surgery may help some patients, even if it does not cure or eliminate all areas of bronchiectasis (Chapter 102). The major indications and goals for surgery in bronchiectasis include removal of destroyed lung partially obstructed by a tumor or the residue of a foreign body; reduction in acute infective episodes occurring in the same pulmonary segment; reduction in overwhelming purulent and viscid sputum production from a specific lung segment; elimination of bronchiectatic airways causing poorly controlled hemorrhage; and removal of an area suspected of harboring resistant organisms, such as MAI or Aspergillus. Surgical intervention is often combined with an aggressive regimen of antibiotics and bronchial hygiene. The immediate goal of surgical extirpation is removal of the most involved segments or lobes with preservation of nonsuppurative or nonbleeding areas. Middle and lower lobe resections are most often performed. Surgical mortality is less than 10%, depending on patient selection. Complications include empyema, hemorrhage, prolonged air leak, and poorly expanding remaining lung due to persistent atelectasis or suppuration. Lung Transplantation Patients with suppurative lung disease were initially considered poor candidates for lung transplantation because of the potential persistence of infection that might worsen during prolonged immunosuppression (Chapter 102). Patients with non-CF bronchiectasis have undergone bilateral lung transplantation. Timing and selection for lung transplantation in patients with bronchiectasis are similar to the guidelines for individuals with CF (Chapter 89). The outcome of lung transplantation in non-CF bronchiectasis includes a 1-year survival rate of 68% and an overall 5-year survival rate of 62%. Double-lung transplantation is required in most patients.