Version January 2024
INTRODUCTION — Bronchiectasis shares many clinical features with chronic obstructive pulmonary disease (COPD), including inflamed and easily collapsible airways, obstruction to airflow, and frequent office visits and hospitalizations. The diagnosis is established clinically on the basis of cough on most days with tenacious sputum production, often one or more exacerbations/year, and radiographically by the presence of bronchial airway dilatation on chest computed tomographic (CT) scans [1].
The epidemiology, major clinical manifestations, and diagnostic approach to bronchiectasis will be reviewed here. The clinical manifestations and treatment of cystic fibrosis lung disease and the treatment of bronchiectasis are discussed separately. (See "Cystic fibrosis: Clinical manifestations of pulmonary disease" and "Cystic fibrosis: Overview of the treatment of lung disease" and "Bronchiectasis in adults: Treatment of acute and recurrent exacerbations".)
EPIDEMIOLOGY — The prevalence of bronchiectasis is provided by independent analyses of International Classification of Diseases (ICD) codes from two large and different United States databases [2,3]. A survey of the United States Medicare population (2012 to 2014) is unique in that ICD codes for bronchiectasis were only accepted from pulmonary specialists [4].
●An estimated 350,000 to 500,000 adults have bronchiectasis in the United States [3].
●The prevalence of bronchiectasis increases with age with an 8- to 10-fold difference in prevalence after the age of 60 years (300 to 500 per 100,000) as compared to ages <40 to 50 years (40 to 50 per 100,000) [2]. Reports from the United Kingdom and Germany describe similar marked age differences in prevalence [5,6]. The Medicare (age ≥65 years) survey of pulmonary specialty-recorded diagnoses had an annual prevalence of 701 per 100,000 persons [4].
●Another approach yields insight into the frequency of bronchiectasis in individuals with chronic cough. From a general population study in Denmark (14,669 individuals), 4 percent had chronic cough (defined as cough lasting >8 weeks) [7]. The greatest risk factor for chronic cough at the individual level among nonsmokers was bronchiectasis with an odds ratio (OR) 5.0, compared with an OR 2.6 for asthma; among former smokers, the OR for bronchiectasis was 7.1.
●Bronchiectasis is more common in women.
●Patients with bronchiectasis use extensive health care resources (eg, frequent ambulatory visits, antibiotic usage, chest CT, hospitalization), and bronchiectasis-associated health care usage has increased [2,4].
●The concomitant presence of chronic obstructive pulmonary disease (COPD) increases the use of health care resources and is associated with poorer health [4].
●In underserved populations, including people living in Alaska, Oceania, and parts of India, bronchiectasis is more prevalent, affects individuals at a younger age, and is associated with decreased survival [8,9]. Social and environmental factors undoubtedly play a role, including smoke exposure, limited access to medical care, and delayed use of antibacterial agents for exacerbations.
PATHOPHYSIOLOGY — Induction of bronchiectasis requires two factors (table 1A-C):
●An infectious insult
●Impaired drainage, airway obstruction, or a defect in host defense
The ensuing host response, immune effector cells (predominantly neutrophils), neutrophilic proteases (elastase), reactive oxygen intermediates (eg, hydrogen peroxide [H2O2]), and inflammatory cytokines, creates transmural inflammation, mucosal edema, cratering, ulceration, and neovascularization in the airways [10]. The following factors may contribute to the pathophysiology of bronchiectasis:
●Effects of neutrophils and neutrophil elastase – Progressive airway destruction in bronchiectasis may be related in part to an abundance of airway neutrophils and unopposed activity of neutrophil elastase. Blood and airway neutrophils in stable bronchiectasis subjects compared with healthy controls have increased viability (reduced apoptosis), reduced phagocytosis, increased release of myeloperoxidase, and impaired bacterial killing (of Pseudomonas) [11]. Pregnancy zone protein (PZP), an intracellular neutrophil protein, has been identified in sputum of bronchiectasis patients and correlates with exacerbations, worsening of symptoms, and the presence of Pseudomonas aeruginosa [12]. Neutrophil extracellular traps (NETs) are extracellular complexes of deoxyribonucleic acid (DNA) fibers containing histone, elastase, PZP, and other inflammatory mediators that are formed as part of a process of neutrophil cell death. NETs trap and kill pathogens, such as bacteria, but may also contribute to the destruction of the major bronchi and bronchiole walls and permanent and abnormal dilation associated with neutrophilic inflammation. NET levels in sputum rise with acute infection and are reduced after intravenous antibiotics for exacerbations (but less so for Pseudomonas as a pathogen) and after a year of low-dose macrolide prophylaxis for exacerbations [13].
●Physical properties of sputum/mucus – The physical properties of sputum differ among patients with cystic fibrosis (CF), those with non-CF bronchiectasis, and healthy controls. Airway mucus from patients with bronchiectasis is more tenacious and concentrated than that of healthy controls, due to higher concentrations of DNA, mucin (MUC5B predominant), and other solids [14]. In physicochemical studies, sputum from Alaska Native children, who have a higher prevalence of bronchiectasis, was less elastic and viscous and had higher transportability than banked sputum of patients with CF and chronic bronchitis [15]. These differences may help explain divergent responses to bronchial hygiene measures. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Airway clearance therapy'.)
●Atopy as driver of inflammation – The presence of atopy conveys a worse clinical course in individuals with chronic obstructive pulmonary disease (COPD) and asthma. In a study of 238 patients with bronchiectasis (excluding allergic bronchopulmonary aspergillosis [ABPA] as etiology) from Scotland, Malaysia, and Singapore, the presence of multiple positive skin prick tests or specific serum immunoglobulin E (IgE) tests was associated with reduced pulmonary function and worse scores on the Bronchiectasis Severity Index [16]. The comparator group for atopy was allergic rhinitis patients with negative CT scans for bronchiectasis.
●Heterozygous variants of the cystic fibrosis transmembrane regulator (CFTR) – Among patients with diffuse bronchiectasis and negative sweat chloride testing, a heterozygous variant of the CFTR gene may contribute to the development of bronchiectasis through dysfunction of the airway sodium and chloride channels [17]. This hypothesis was examined in a study that assessed nasal transepithelial potential difference in patients with diffuse bronchiectasis, a normal sweat chloride, and either a normal CFTR genotype, or one or two CFTR mutations (eg, a loss of function mutation on one chromosome and a mild mutation on the other), and compared the results with those in normal subjects and patients with known CF [17]. The nasal potential difference test reflects the function of sodium and chloride channels in the airway epithelium. An abnormal nasal electrophysiologic phenotype, intermediate between normal and CF values, was identified in patients with diffuse bronchiectasis and one CFTR mutation, suggesting that the presence of a single CFTR mutation may play a role in the development of diffuse bronchiectasis.
●Vitamin D deficiency – A potential role of vitamin D deficiency in the vicious cycle of recurrent exacerbations of bronchiectasis was examined in an observational study of 402 patients with bronchiectasis, who were followed for three years [18]. At baseline, 50 percent were vitamin D deficient (25 hydroxy-vitamin D levels <25 nmol/L), and another 43 percent were insufficient (25 hydroxy-vitamin D <75 nmol/L). The vitamin D-deficient patients (compared with the insufficient and sufficient patients) were more likely to have sputum colonization with bacteria including Pseudomonas, more frequent exacerbations (including those needing hospitalization), worse respiratory symptoms as assessed by standard questionnaires, and increased sputum markers of neutrophil inflammation. It is not known whether this association reflects an effect of vitamin D on innate immunity or reduced outdoor physical activity due to more severe disease.
●Common variable immunodeficiency (CVID) – Small airway changes have been described before the advanced and destructive manifestations of bronchiectasis become apparent in patients with CVID. As an example, inspiratory and expiratory high-resolution computed tomography (HRCT) scans were performed on 54 children ages 6 to 18 years with CVID in a stable state [19]. The most common abnormality was expiratory air trapping (mosaic attenuation), which was seen in 71 to 80 percent and was the only abnormality in 9 to 15 percent. The presence of air trapping on expiratory, but not inspiratory, views suggests that airway inflammatory changes are the cause and raises the possibility that these changes are reversible. (See "Common variable immunodeficiency in children", section on 'Pulmonary manifestations' and "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults", section on 'Pulmonary disease'.)
ETIOLOGIES — There are numerous etiologies that can induce or contribute to the pathophysiologic processes that result in bronchiectasis (table 1A-C) [20-22]. They include airway obstruction (eg, foreign body aspiration), defective host defenses, cystic fibrosis (CF), Young syndrome, rheumatic and systemic diseases, primary ciliary dyskinesia, pulmonary infections, and allergic bronchopulmonary aspergillosis (ABPA). The frequency of the different etiologies varies with the geographic location and referral population, as shown in the following studies:
●In a North American referral center population, a comprehensive evaluation of 112 patients with bronchiectasis confirmed on chest CT identified a specific etiology in 93 percent [20]. The most common etiologies were rheumatic disease (eg, rheumatoid arthritis, Sjögren's disease, Crohn disease), ABPA, immunodeficiency, hematologic malignancy, aspiration, and nontuberculous mycobacterial infection.
●A report from the European Bronchiectasis Network (EMBARC) comprising academic medical center databases in Europe identified an underlying cause of bronchiectasis in 60 percent of nearly 17,000 patients, including postinfection (21 percent; includes previous pneumonia, remote childhood infections, and pertussis), chronic obstructive pulmonary disease (COPD; 8.1 percent), mycobacterial disease (5.9 percent), rheumatic disorders (4.8 percent), and immunodeficiency (4.1 percent) [23]. Testing that followed British Thoracic Society guidelines [24] identified an etiology that would potentially lead to genetic testing (eg, alpha-1 antitrypsin deficiency) or a change in management (eg, replacement therapy for immunodeficiency, specific treatment of ABPA, prevention of aspiration, treatment of focal obstruction, or aggressive bronchial hygiene in ciliary dyskinesia) in 13 percent.
●An underlying etiology is often identified in children and adolescents. In a systematic review of 989 patients with non-CF bronchiectasis, ages 21 years and younger, an etiology was identified in 623 (63 percent) [25]. Of greater importance, 35 percent of these patients had immunodeficiency (primary and secondary), aspiration/foreign body, or ciliary dyskinesia, conditions in which specific management strategies may improve the outcome.
Airway obstruction — Focal airway obstruction can be caused by foreign body aspiration, an intraluminal obstructing lesion such as a carcinoid tumor, or extraluminal compression from encroaching lymph nodes [26]. A case report demonstrated focal bronchiectasis 3.5 years after placement of lung volume reduction coils for emphysema [27]. It is important to identify the presence of airway obstruction because surgical resection is often curative.
Bronchiectasis that results from foreign body aspiration generally occurs in the right lung and in the lower lobes or the posterior segments of the upper lobes. As an example, toddlers (ages one to three years) may aspirate seeds, popcorn, or unchewed food. An episode of choking, coughing, or unexplained wheezing or hemoptysis should raise the suspicion of a foreign body. A retrospective study found that, among children with greater than one month of respiratory symptoms and middle lobe or lingula abnormalities on chest radiograph, an early and aggressive strategy of chest CT and bronchoscopy with cultures led to interventions (eg, foreign body removal, infection treatment) that produced favorable outcomes, including reduced bronchiectasis [28]. (See "Airway foreign bodies in children".)
In adults, particulate aspiration is typically associated with an altered state of consciousness (due to stroke, seizures, intoxication, or emergent general anesthesia). The foreign body is often unchewed food or part of a tooth or crown. A postobstructive pneumonia may follow the aspiration event, often resulting in incomplete resolution and predisposition to subsequent lung abscess. Delayed or ineffective therapy and poor nutrition may contribute to prolonged pneumonitis with resultant focal bronchiectasis (figure 1). (See "Airway foreign bodies in adults".)
Esophageal reflux contributes to asthma and interstitial lung disease. The same concern or association applies to bronchiectasis [29].
Tracheobronchomalacia and tracheobronchomegaly — Anatomic defects of the airways, such as tracheomalacia, deficiency of cartilage in fourth to sixth order bronchi (Williams-Campbell syndrome) (image 1), bronchomalacia, and tracheobronchomegaly, can lead to bronchiectasis via deficient clearance of respiratory secretions and recurrent infections [30]. While the airways appear dilated on imaging studies, the deficient cartilage support results in airway collapse during forced exhalation. Chest CT with expiratory views will show proximal airway collapse and narrowing. Tracheomalacia, bronchomalacia, and tracheobronchomalacia refer to diffuse or segmental weakness of the trachea and/or mainstem bronchi and are discussed separately. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation".)
Tracheobronchomegaly (eg, Mounier-Kuhn syndrome) can be diagnosed when the diameter of the trachea (measured 2 cm above the main carina), right mainstem bronchus, and left mainstem bronchus exceed a diameter two standard deviations above normal [31]. As a general rule, tracheomegaly is likely present when the lower trachea is wider than the vertebral column at that level. More precisely, airway diameters exceeding the following are abnormal: trachea >3 cm, a right mainstem bronchus >2.5 cm, and a left mainstem bronchus >2 cm. (See "Radiology of the trachea", section on 'Tracheobronchomegaly'.)
Defective host defenses — Impairment in host defenses may be local, as with ciliary dyskinesia [32], or systemic, as with hypogammaglobulinemia, or prolonged immunosuppression (eg, in transplant patients and patients with rheumatic disorders on biologic disease-modifying agents) [33-35]. The mechanism of bronchiectasis is likely bronchial wall injury from repeated infections [33]. (See 'Primary ciliary dyskinesia' below.)
Patients with hypogammaglobulinemia (eg, x-linked) usually present in childhood with repeated sinopulmonary infections; however, middle-aged adults have been identified with few or no recognized previous respiratory infections [36,37]. Hypogammaglobulinemia may also be associated with thymoma [38]. Immunoglobulin quantitation is included in the diagnostic evaluation of the patient with bronchiectasis, since gamma globulin replacement can diminish or prevent further respiratory tract infections and lung damage. (See "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults", section on 'Evaluation' and "Treatment and prognosis of common variable immunodeficiency", section on 'Immune globulin replacement therapy'.)
Isolated IgG subclass deficiency (in the presence of normal or near-normal levels of total IgG) as a cause of bronchiectasis is controversial due to variable ranges of values even in healthy individuals. In a multicenter study of young children from the Netherlands, 49 with IgG subclass deficiency (mainly IgG2) and reduced antibody response to a polysaccharide antigen were identified and followed [39]. At least five of the children (10 percent) had bronchiectasis at an average age of seven years. To help determine whether a low IgG subclass represents immunodeficiency, a challenge with common humoral bacterial antigens (eg, Haemophilus influenzae vaccine or pneumococcal vaccine), followed six weeks later by measurement of antibody titers, can be performed [40,41]. (See "Primary humoral immunodeficiencies: An overview".)
Milder cases of autosomal recessive chronic granulomatous disease may present in adulthood. Extrapulmonary infections such as cellulitis, cutaneous abscesses, lymphadenitis, and osteomyelitis are common in these patients. The majority of infections are due to Staphylococcus aureus, Burkholderia (formerly Pseudomonas) cepacia, Serratia marcescens, Nocardia, and Aspergillus. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis".)
Cystic fibrosis — Clinical disease requires pathogenic mutations in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although formerly considered a disease of childhood, up to 7 percent of patients with cystic fibrosis (CF) are diagnosed at age 18 years or older [42]. Sinusitis and bronchiectasis are the major respiratory manifestations of CF, and the latter may be the sole feature of CF in adults. (See "Cystic fibrosis: Clinical manifestations and diagnosis".)
Clues suggesting the presence of this disorder include upper lobe radiographic involvement and sputum cultures showing mucoid P. aeruginosa [43]. When CF is diagnosed after the age of 20 years, homozygosity at the delta F508 locus in the CFTR gene is less common than in children and non-delta F508 mutations are more common. (See "Cystic fibrosis: Genetics and pathogenesis".)
A positive sputum culture for mucoid P. aeruginosa in the year of diagnosis is more common in adults than children with CF, while a positive culture for nonmucoid P. aeruginosa is more common in children [43]. Adults also have increased colonization with nontuberculous mycobacteria [43-45]. Pancreatic insufficiency and diabetes mellitus are less common when CF is discovered after age 20 years than before.
The diagnosis of CF can usually be established by demonstrating an elevated sweat chloride concentration (≥60 mmol/L; values of 30 to 60 require additional testing), which is performed at specialized centers [42,43]. Patients who present with CF as adults may have intermediate or normal sweat chloride results. Screening for mutations in the CFTR gene may be required to confirm the diagnosis [42]. Measurement of the potential difference across the nasal epithelium, available in specialized centers, is sometimes used to corroborate the diagnosis [17,43]. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Sweat chloride' and "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Molecular diagnosis' and "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Nasal potential difference measurements'.)
Individuals with a single pathogenic mutation CFTR Phe508del (carriers) may be at increased risk of pulmonary disease in adulthood (eg, bronchiectasis, chronic bronchitis), depending on environmental exposures (eg, cigarette smoking) and other genetic risk factors (eg, variants in epithelial sodium channel genes) [7,46,47]. Individuals with bronchiectasis and a single Phe508del mutation are considered to have a CFTR-related disorder, which is discussed separately. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'CFTR-related disorder'.)
Young syndrome — Young syndrome describes patients with bronchiectasis, sinusitis, and obstructive azoospermia who have no evidence of CF. As the frequency of this diagnosis has declined to almost nonexistent, some experts have suggested that exposure to mercury in childhood may have been a cause of Young syndrome in men born before 1955 [48]. Another possibility is that some cases attributed to Young syndrome are actually cases of primary ciliary dyskinesia (PCD). Now that better diagnostic methods are available, these cases can be correctly identified as forms of PCD. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)" and "Causes of male infertility", section on 'Sperm transport disorders'.)
Rheumatic and other systemic diseases — Two rheumatic diseases, rheumatoid arthritis (RA) [49-51] and Sjögren's disease [52], can be complicated by bronchiectasis. Arthropathy and sicca features are usually advanced when bronchiectasis becomes apparent. In some cases, however, bronchiectasis occurs before the rheumatic disease. The association of RA and bronchiectasis is accompanied by a higher mortality than other bronchiectasis associations except COPD [53]. (See "Overview of pleuropulmonary diseases associated with rheumatoid arthritis", section on 'Bronchiectasis'.)
The mechanism underlying bronchiectasis in patients with RA and Sjögren's disease is not known. In a family-based association study, the frequency of an abnormal CF gene (CFTR) allele was increased in patients with bronchiectasis and RA relative to patients with RA but without bronchiectasis and normal controls [54]. (See 'Pathophysiology' above.)
Bronchiectasis has been noted in association with other systemic diseases, such as inflammatory bowel disease, more frequently in ulcerative colitis than in Crohn disease, and the yellow nail syndrome [55,56]. (See "Pulmonary complications of inflammatory bowel disease".)
Primary ciliary dyskinesia — Primary ciliary dyskinesia was originally described in the respiratory tract and sperm of patients with Kartagener syndrome (situs inversus, sinusitis, bronchiectasis), but situs inversus is present in only half of patients with dyskinetic cilia and related poor mucociliary clearance, repeated sinopulmonary infections, and subsequent bronchiectasis [32,57,58]. Nasal nitric oxide analysis, although not widely available, is a useful screening test for PCD; low levels (eg, 77 nL/minute) are consistent with PCD [59]. An extended panel genetic testing (>12 genes) is available for the most frequently associated genetic abnormalities [60,61]. An epithelial (nasal or bronchial) brush or biopsy may be useful but requires labor-intensive testing to assess ciliary motion and ultrastructure. The diagnosis and management of PCD are described separately. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)", section on 'Nasal nitric oxide' and "Primary ciliary dyskinesia (immotile-cilia syndrome)", section on 'Genetic testing'.)
Further evidence of the relationship between bronchiectasis and dyskinetic cilia comes from patients with autosomal dominant polycystic kidney disease (ADPKD), a disease in which renal cysts develop because of defective cilia and ciliary protein expression (polycystin-1 and polycystin-2) [62,63]. Immunostaining of lung tissue from non-ADPKD patients reveals that the motile cilia of airway epithelial cells express polycystin-1, suggesting that absent polycystin-1 in patients with ADPKD might be a risk factor for airway damage [62]. In a retrospective review of chest CT scans, 34 out of 92 patients with ADPKD had bronchiectasis (37 percent) compared to 12 out of 93 patients with non-ADPKD chronic renal disease (13 percent), a difference that was statistically significant [62]. In autopsy examinations, the lungs from one of five patients with ADPKD had histologic evidence of bronchiectasis.
Alpha-1 antitrypsin deficiency — Emphysema is the main lung disease recognized in alpha-1 antitrypsin deficiency. However, a review of the clinical manifestations and chest CT scans of 74 patients with alpha-1 antitrypsin deficiency found that 70 had radiographic abnormalities suggestive of bronchiectasis (95 percent) and 20 had regular sputum production (27 percent) [64]. These observations support current guidelines that recommend alpha-1 testing in patients with bronchiectasis and no other evident etiology [65]. (See "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency".)
Pulmonary infections — A spectrum of bacterial, mycobacterial, atypical bacterial, and viral lung infections have been associated with the development of bronchiectasis.
●Childhood infections – Childhood lung infections (eg, bacterial, viral, and mycoplasma pneumonia and protracted bacterial bronchitis) have been implicated in the pathogenesis of bronchiectasis [66]. In a case series of 38 children with mycoplasma pneumonia, eight children had evidence of bronchiectasis on high-resolution computed tomography (HRCT) obtained one to two years later [66]. In a cohort study, 161 children with protracted bacterial bronchitis (history of >4 weeks of wet cough, treatment with amoxicillin for two weeks, and no evidence for other causes of cough) were followed for two years, and 8 percent developed bronchiectasis [67]. Risk factors were infection by Haemophilus influenzae and recurrent episodes of bacterial bronchitis. Childhood whooping cough (pertussis) is largely of historical interest [66]. (See "Pertussis infection in adolescents and adults: Clinical manifestations and diagnosis" and "Pertussis infection in infants and children: Clinical features and diagnosis".)
●Adult infections – Virulent pneumonias in adults due to viruses and bacteria (such as S. aureus) has been recognized as precursors to bronchiectasis [68]. Advanced bronchiectasis has been reported after widespread severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia [69-71]. One report mentions that S. aureus may have been a copathogen similar to what has been known regarding the association of S. aureus with influenza virus [69]. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'S. aureus'.)
●Mycobacterial infections – In addition to direct tissue injury, a sequela of virulent infections (such as tuberculosis) may include enlarged and caseous lymph nodes around bronchi or damaged airways that predispose to bacterial colonization [72,73]. In a Korean study, 9 percent of 1409 individuals who underwent chest CT for health screening (mostly for lung cancer) had bronchiectasis; a previous history of tuberculosis was significantly associated with bronchiectasis [72].
Nontuberculous mycobacteria (NTM) have traditionally been considered a secondary pathogen in an immunocompromised host (acquired immunodeficiency syndrome [AIDS]) or in a previously damaged lung (bullous emphysema). However, apparently healthy individuals (primarily nonsmoking women over the age of 50 years) may develop bronchiectasis due to primary NTM infection. Similar to a sputum smear showing acid-fast bacilli and a culture confirming the presence of NTM, a CT scan of the chest is relatively specific, showing small irregular nodules, often in the middle lobe or lingula [74-76]. Patients with bronchiectasis and NTM infection are more likely to have aspergillus-related lung disease (including ABPA) than patients with bronchiectasis who do not have NTM infection [77].
Mycobacterium avium complex (MAC) are the most frequently identified NTMs. Evidence of the pathogenicity of MAC comes from a surgical series of nine patients with positive sputum cultures for MAC [78]. Examination of resected lung tissues revealed MAC, bronchiectasis, and granulomata. (See "Epidemiology of nontuberculous mycobacterial infections" and "Diagnosis of nontuberculous mycobacterial infections of the lungs" and "Treatment of Mycobacterium avium complex pulmonary infection in adults".)
●Nocardia – Nocardia may be a contributory pathogen in bronchiectasis. In a retrospective review, Duke University investigators identified 183 patients with positive cultures for Nocardia species between 1996 and 2013 [79]. Of these, 40 (22 percent) had bronchiectasis, and the incidence of Nocardia appeared to increase over time.
Allergic bronchopulmonary aspergillosis — Allergic bronchopulmonary aspergillosis (ABPA) should be suspected in patients with a long history of asthma that is resistant to bronchodilator therapy and associated with a cough often productive of sputum that is mucopurulent or contains mucous plugs. ABPA may also be seen in COPD, particularly when there are features of asthma [80]. Sputum cultures may be positive for Aspergillus species. Chest CT scans show peripheral and central airway bronchiectasis, which is unusual in patients with bronchiectasis caused by other disorders [81]. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis".)
ABPA probably represents a hyperimmune reaction to the Aspergillus organism, rather than a true infection, and is characterized by an exaggerated T helper cell response. Immunologic features of ABPA include blood eosinophilia, very high plasma IgE levels, and precipitating and specific antibodies to Aspergillus [81].
Asthma — An interrelationship between asthma and bronchiectasis is suspected, even in the absence of ABPA. Patients with bronchiectasis may wheeze and have bronchial hyperresponsiveness without meeting the criteria for asthma, but there may be a specific phenotype of bronchiectasis with asthma (similar to the concept of asthma-COPD overlap) that represents an independent risk factor for frequent exacerbations. In a database survey, asthma (diagnosed based on clinical characteristics and reversible airflow limitation per international guidelines) was an independent risk factor for bronchiectasis exacerbations [82].
Bronchial thermoplasty (BT), a treatment for severe asthma, was associated with a 7 percent incidence of new bronchiectasis on chest CT (not seen before BT), based on data from a multicenter registry of patients enrolled in large clinical trials of BT and followed for 10 or more years [83]. This observation is intriguing because one of the physiologic effects of bronchial thermoplasty is airway dilation, a chest CT diagnostic criterion for bronchiectasis. It is also unknown how many of the asthmatic patients might have developed bronchiectasis during this lengthy follow-up independent of the procedure. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Treatment of severe asthma in adolescents and adults", section on 'Bronchial thermoplasty'.)
Cigarette smoking and COPD — A causal role for cigarette smoking in bronchiectasis has not been demonstrated. However, cigarette smoking, the presence of chronic obstructive pulmonary disease (COPD), and repeated infections or exacerbations may worsen pulmonary function and accelerate the progression of disease that is already present [84-89].
A quantitative CT study that compared smokers with bronchiectasis (based on imaging) to healthy nonsmokers has raised the hypothesis that an increased bronchus-to-artery ratio in smokers may be due to arterial constriction (hypoxemia) rather than bronchial dilation [90]. In this study, bronchial and adjacent arterial diameters were measured on HRCT images of "bronchiectatic" and normal airways. The arterial diameters in the "bronchiectatic" areas were smaller than those in nonbronchiectatic areas.
CLINICAL FEATURES — The classic clinical manifestations of bronchiectasis are cough most days of the week, production of mucopurulent and tenacious sputum most days of the week for months to years, and a history of exacerbations [1,91,92]. The older literature also described "dry bronchiectasis" with episodic hemoptysis and no sputum production, but this presentation is less common.
Other, less specific complaints include dyspnea, wheezing, and pleuritic chest pain. Patients often report frequent bouts of "bronchitis" requiring therapy with repeated courses of antibiotics. There is generally a past history of repeated respiratory tract infections over several years, although a single episode of severe bacterial pneumonia, pertussis, or tuberculosis can also result in bronchiectasis. (See 'Etiologies' above.)
In a retrospective chart review of 103 patients with bronchiectasis who presented to a referral center, the following clinical findings were documented [93]:
●Symptoms – cough (98 percent of patients), daily sputum production (78 percent), dyspnea (62 percent), rhinosinusitis (73 percent), hemoptysis (27 percent), and recurrent pleurisy (20 percent)
●Physical findings – crackles (75 percent) and wheezing (22 percent) were common, with digital clubbing occurring in only 2 percent of patients
Several validated questionnaire instruments encompassing key respiratory issues and general health quality have been useful as outcome measures in clinical research. They include new ones specifically for bronchiectasis (eg, Quality Of Life-Bronchiectasis, Bronchiectasis Health Questionnaire) or adapted from chronic obstructive pulmonary disease (COPD; eg, St. George Respiratory Questionnaire [SGRQ], COPD Assessment Test, Leicester Cough Questionnaire) [94]. Experience with the SGRQ is most extensive. The COPD Assessment Test (CAT) is the most facile with fewer questions and can easily be adapted to longitudinal clinical practice [95-97].
Although respiratory complaints are prominent, other symptoms can be annoying and distressing. Fatigue was noted in 43 percent of 117 bronchiectasis patients using a validated fatigue impact scale. The presence of fatigue correlated with lower forced expiratory volume in one second (FEV1) values, but not the presence of P. aeruginosa in sputum [98]. Seventy-five women attending a respiratory clinic were evaluated for urinary incontinence and its effect on their qualities of life [99]. The prevalence of urinary incontinence in the patients with bronchiectasis was 47 percent, compared to an estimated prevalence of 10 to 12 percent in the general population. Many of these patients were reluctant to discuss such complaints. Identification and treatment of urinary incontinence can improve or relieve this symptom [100].
Among patients with bronchiectasis, a reduced sense of smell is common. In a study of 91 patients with bronchiectasis, a significant reduction in sense of smell was noted in patients with a history of chronic rhinosinusitis (with or without associated nasal polyps) and/or primary humoral immunodeficiency [101]. Reduced bone mineral density, osteopenia, and even osteoporosis have been found in patients with non-cystic fibrosis (CF) bronchiectasis [102]. Comparisons were made with retrospective controls. The reduced bone mineral density was particularly noteworthy in the younger (<45 years of age) subjects.
DIAGNOSTIC EVALUATION — The diagnosis of bronchiectasis should be suspected in patients with persistent or recurrent production of mucopurulent or purulent sputum [91]. The purpose of a diagnostic evaluation is radiographic confirmation of the diagnosis, identification of potentially treatable causes and microbiologic pathogens, and functional assessment (table 1A-C) [24]. The evaluation consists of laboratory testing, radiographic imaging, and pulmonary function testing.
Laboratory tests — The following studies are typically part of the initial evaluation of a patient with bronchiectasis [103]:
●A complete blood count with differential. Elevated blood platelets (>400 x 109/L in a stable state) are associated with increased mortality, increased hospitalizations for exacerbations, poor quality of life by questionnaire, and increased severity by the Bronchiectasis Severity Index [104]. Elevated eosinophils may identify an endotype that has treatment implications as seen in asthma and chronic obstructive pulmonary disease (COPD) [105,106]. (See "Bronchiectasis in adults: Maintaining lung health".)
●Immunoglobulin quantitation to measure the levels of the immunoglobulins IgG, IgM, and IgA. (See "Primary humoral immunodeficiencies: An overview" and "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults".)
●Testing for cystic fibrosis (CF): Sweat chloride and/or mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. (See 'Cystic fibrosis' above.)
●Sputum smear and culture for bacteria, mycobacteria, and fungi.
Additional tests that are obtained in the appropriate setting may include (table 1A-C) (see 'Etiologies' above):
●Specific aspergillus IgE and IgG antibodies, total serum IgE level (see 'Allergic bronchopulmonary aspergillosis' above and "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis", section on 'Diagnosis')
●IgG subclass levels (see "IgG subclass deficiency", section on 'Evaluation')
●Antibody titers to pneumococcal serotypes before and four weeks after vaccination with polysaccharide pneumococcal vaccine (see "Assessing antibody function as part of an immunologic evaluation", section on 'Adults and children over two years')
●Alpha-1 antitrypsin level and/or genotype (see 'Alpha-1 antitrypsin deficiency' above)
●Rheumatoid factor
Cell counts of induced sputum are being evaluated as a way to identify patients with bronchiectasis. In a retrospective series of patients with stable obstructive airways disease who had a high-resolution computed tomography (HRCT) available for analysis, sputum leukocytosis and neutrophilia were more common in those with radiographic bronchiectasis than those without (mean 48.2 x 106 versus 12.6 x 106 cells/gram of sputum and 78.2 versus 64.4 percent neutrophils) [107]. Performing cell counts on induced sputum is labor intensive and would require more study prior to widespread implementation.
Chest radiograph — The chest radiograph is abnormal in most patients with bronchiectasis. Suspicious but nondiagnostic radiographic findings include linear atelectasis, dilated and thickened airways (ie, tram or parallel lines, ring shadows on cross section) (image 2A-B), and irregular peripheral opacities that may represent mucopurulent plugs.
Computed tomography — Noncontrast chest CT has become the definitive study to confirm the diagnosis of bronchiectasis. The vast majority of computed tomography (CT) scanners are now multidetector computed tomography (MDCT) scanners, which can obtain thin sections of ≤1 mm (high resolution) with high spatial frequency. MDCT is the preferred imaging modality for bronchiectasis [91,108]. HRCT originally referred to scanners that obtained images of 1 to 1.5 mm collimation slices every 10 mm. (See "High resolution computed tomography of the lungs".)
MDCT (or HRCT if MDCT is not available) is indicated in the following settings:
●There are suspicious clinical findings but a relatively normal chest radiograph.
●The chest radiograph has abnormal findings (eg, persistent consolidative opacity or thickened airways) and bronchiectasis is strongly suspected.
●Management decisions must be made that depend upon the extent of bronchiectasis. As an example, mapping of the chest is needed to define suspected abnormal areas and to demonstrate absent or minimal involvement in the rest of the lung if surgical resection is being contemplated.
●The presence (or absence) of confounding diseases needs to be defined, such as chronic obstructive lung disease, interstitial lung disease, or malignancy.
Features — The major features of bronchiectasis on HRCT or MDCT include [1,91]:
●Airway dilatation, which can be detected as parallel (tram) lines or end-on ring shadows (image 3). An airway lumen diameter ≥1.5 times the adjacent vessel (called airway-artery or bronchoarterial ratio) is indicative of cylindrical bronchiectasis. The "signet-ring" sign, which is a classic feature of bronchiectasis, refers to the appearance in cross-section of a dilated, air-filled bronchus that is contiguous with the smaller nodular opacity of a pulmonary artery (the jewel on the ring) [108].
●Lack of tapering towards the periphery of the chest in combination with dilatation may be more specific than bronchial dilatation alone because some healthy individuals and patients with asthma may have areas of bronchial dilatation.
●Airway visibility within 1 cm of a costal pleural surface or touching the mediastinal pleura.
●Airways affected by bronchiectasis may contain mucopurulent plugs or debris accompanied by postobstructive air trapping. When small airways are affected, peripheral, irregular, short (2 to 4 mm) linear branching markings are noted and the term "tree-in-bud pattern" is applicable (image 4). Although tree-in-bud may acutely reflect aspiration and/or bacterial infection, persistence of findings is suspicious for bronchiectasis distinctly associated with nontuberculous mycobacteria (NTM) infection [109].
●Cysts off the bronchial wall are a feature of more destructive bronchiectasis (image 5). In heavily involved areas, the cysts are clustered to appear like grapes (cystic bronchiectasis) (image 6). Blebs, seen in emphysema, are thinner walled and not accompanied by proximal airway changes.
Although not characteristic of bronchiectasis, other abnormalities may be seen on HRCT, none of which are diagnostic of bronchiectasis:
●Consolidation of a segment or lobe (from pneumonia).
●Enlarged lymph nodes, likely a reaction to infection.
●Areas of low attenuation and vascular disruption (mosaic pattern). This is probably due to the distorting effect of an inflammatory process in small airways.
Distribution — The distribution of bronchiectasis may be important diagnostically. A central (perihilar) distribution is suggestive of allergic bronchopulmonary aspergillosis (ABPA); predominant upper lobe distribution is characteristic of CF or one of its variants; middle and lower lobe distribution is consistent with primary ciliary dyskinesia (PCD); middle lobe and lingular segment of the left upper lobe involvement is characteristic of NTM; and lower lobe involvement is typical of idiopathic bronchiectasis [110-113] (image 7A-C).
Another confounding diagnosis is the "traction bronchiectasis" seen in pulmonary fibrosis (image 8). When the lung parenchyma is distorted by fibrosis, the airways can be dilated or pulled to simulate bronchiectasis; in this setting, however, the other features of bronchiectasis are absent.
Severity — Various grading or scoring systems have been proposed to correlate the extent of bronchiectasis on HRCT with disease severity; however, none of these systems has been validated prospectively or with large patient populations [114-117].
●One group performed serial HRCTs and spirometry on 48 patients with bronchiectasis, with follow-up ranging from 6 to 74 months [115]. HRCT evidence of mucous plugging (potentially reversible) and bronchial wall thickening best correlated with decline in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
●Among patients with COPD, coexisting MDCT evidence of bronchiectasis is associated with increased severity of COPD exacerbations. In a two-year follow-up study of 54 patients with stable COPD, 27 patients (50 percent) had coexisting lower lobe bronchiectasis [117]. Compared with patients without bronchiectasis, patients with bronchiectasis had a longer duration of symptoms during exacerbations, a greater burden of potentially pathogenic bacteria in the lower airway, and increased sputum inflammatory markers, including interleukin (IL)-8 and IL-6 [117].
●In the largest of this type of study, bronchiectasis severity on HRCT scans was studied in 184 patients from Scotland [118]. The degree of bronchial dilatation and number of segments with emphysema (adapted from the Bhalla scoring system used in CF) correlated with clinical parameters of severity including FEV1 percent predicted, sputum purulence, and hospitalizations for exacerbations. The radiologic scoring system was then validated in 302 patients from six bronchiectasis centers in Great Britain and Europe. Simplified HRCT scoring systems in combination with clinical parameters may help predict disease severity.
Lung function tests — Pulmonary function testing is used for functional assessment of impairment due to bronchiectasis. Spirometry before and after the administration of a bronchodilator is satisfactory in most patients. Obstructive impairment (ie, reduced or normal FVC, low FEV1, and low FEV1/FVC) is the most frequent finding, but a low FVC may indicate air trapping with lung volumes needed to confirm a high residual volume (RV) and high RV/TLC [119]. (See "Overview of pulmonary function testing in adults".)
The six-minute walk and incremental shuttle walk tests [120] may provide additional information to spirometry (eg, FEV1) [121]. In a study of 27 patients with bronchiectasis, the six-minute walk test distance correlated more closely with quality of life (St. George Respiratory Questionnaire and Short Form 36) than the physiologic tests [122].
The Lung Clearance Index (LCI; multiple breath washout) is another method to measure airflow limitation, but it is only available in specialized laboratories. In bronchiectasis, the LCI is reproducible, may be more sensitive than the FEV1, and correlates better with CT abnormalities than FEV1 [123]. (See "Cystic fibrosis: Clinical manifestations of pulmonary disease", section on 'Pulmonary function testing'.)
Impulse oscillometry is a technique that uses pressure oscillations generated at the mouth to assess airway resistance. In a study of 100 patients with bronchiectasis, impulse oscillometry measures of airway resistance correlated with mild impairment as judged by low HRCT scores, suggesting this test may be a better index of early or mild bronchiectasis than FEV1. Impulse oscillometry did not correlate with exacerbations or more severe impairment [124]. Further study is needed before this technique is incorporated into routine assessment of bronchiectasis.
One analysis of patients with bronchiectasis followed every four months for a year found that FEV1 and certain health-associated quality-of-life measures had low variability in patients with clinically stable disease, making them amenable to follow longitudinally in both clinical and research settings [125]. LCI and C-reactive protein showed greater test-to-test variability than these other measures.
Other studies — For patients suspected of having primary ciliary dyskinesia, the history will dictate what tests will help confirm the diagnosis (eg, family history, infertility, situs inversus) [57,126]. (See "Primary ciliary dyskinesia (immotile-cilia syndrome)", section on 'Diagnostic evaluation'.)
Flexible bronchoscopy may be needed when sputum studies are negative and mycobacteria or a focal obstructing lesion are suspected. (See 'Airway obstruction' above.)
DIAGNOSIS — The diagnosis of bronchiectasis is based on a combination of clinical and CT features [1,91]. Clinical features indicative of clinically significant bronchiectasis include cough on most days of the week, sputum production on most days of the week, and a history of exacerbations (see 'Clinical features' above). CT features that are reliable signs of bronchiectasis include the following (see 'Computed tomography' above):
●Airway-to-arterial ratio ≥1.5 (internal airway lumen diameter/adjacent pulmonary artery diameter)
●Lack of tapering of bronchi (tram track appearance)
●Airway visibility within 1 cm of a costal pleural surface or touching the mediastinal pleura
Once a diagnosis of bronchiectasis is made, efforts should be directed at determining the underlying cause (table 1A and table 1B and table 1C). (See 'Etiologies' above and 'Laboratory tests' above.)
BRONCHIECTASIS REGISTRIES — Research registries in the United States, Europe, and the United Kingdom have been established to gather key patient-related diagnostic and therapeutic features. These registries are available for multicenter research studies [74,127-129].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchiectasis" and "Society guideline links: Primary ciliary dyskinesia".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Allergic bronchopulmonary aspergillosis (The Basics)" and "Patient education: Coughing up blood (The Basics)" and "Patient education: Bronchiectasis in adults (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Pathophysiology – Bronchiectasis is an acquired disorder of the major bronchi and bronchioles that is characterized by permanent abnormal dilatation and destruction of bronchial walls. The induction of bronchiectasis requires an infectious insult plus impairment of drainage, airway obstruction, and/or a defect in host defense. (See 'Pathophysiology' above.)
●Causes – There are numerous etiologies that can induce or contribute to the pathophysiologic processes that result in bronchiectasis. They include airway obstruction (eg, foreign body aspiration), defective host defenses, cystic fibrosis (CF), rheumatic and systemic diseases, dyskinetic cilia, pulmonary infections, and allergic bronchopulmonary aspergillosis (ABPA). (See 'Etiologies' above.)
●Clinical features – The classic clinical manifestations of bronchiectasis are cough on most days of the week, daily production of mucopurulent and tenacious sputum for months to years, and a history of exacerbations. Less specific complaints include dyspnea, hemoptysis, wheezing, and pleuritic chest pain. (See 'Clinical features' above.)
●Evaluation – The purpose of the diagnostic evaluation is confirmation of the diagnosis on chest imaging, identification of potentially treatable causes, and functional assessment. The evaluation consists of laboratory and microbiologic testing, radiographic imaging, and pulmonary function testing (table 1A-C). (See 'Diagnostic evaluation' above.)
The initial evaluation of a patient with bronchiectasis should include a complete blood count with differential, immunoglobulin quantitation (IgG, IgM, and IgA), and sputum culture and smear for bacteria, mycobacteria, and fungi. (See 'Laboratory tests' above.)
●Imaging – The chest radiograph is abnormal in most patients with bronchiectasis. However, CT of the chest is the defining test of bronchiectasis. Characteristic CT features of bronchiectasis include airway dilatation (airway lumen-artery diameter ratio ≥1.5), lack of airway tapering (parallel or "tram" line appearance), and airway visibility at the lung periphery. Bronchial wall thickening, cystic dilation of bronchi, and mucopurulent plugs or debris accompanied by air trapping may be observed. (See 'Chest radiograph' above and 'Computed tomography' above.)
●Pulmonary function testing – Pulmonary function testing is used for functional assessment of impairment due to bronchiectasis. Obstructive impairment (ie, reduced or normal forced vital capacity [FVC], low forced expiratory volume in one second [FEV1], and low FEV1/FVC) is the most frequent finding. (See 'Lung function tests' above.)
●Diagnosis – The diagnosis of bronchiectasis is established based on the combination of typical clinical features and characteristic CT features of bronchial airway dilatation. (See 'Diagnosis' above.)
●Bronchiectasis registries – Bronchiectasis research consortia and registries have been established to gather key patient-related diagnostic and therapeutic features. (See 'Bronchiectasis registries' above.)
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