Bronchiectasis is a chronic respiratory condition characterized by irreversible widening and damage to the bronchi, the airways that carry air to and from the lungs, resulting in impaired mucociliary clearance, mucus accumulation, and recurrent infections.[1] This structural abnormality leads to a cycle of inflammation and further bronchial destruction, distinguishing it from reversible airway diseases like asthma.[2]The condition often develops following severe or repeated lung infections, such as those caused by bacteria, viruses, or fungi, or due to underlying disorders including cystic fibrosis, primary ciliary dyskinesia, immunodeficiency, or aspiration.[3] Post-infectious bronchiectasis is a common form, particularly in regions with high tuberculosis prevalence, while non-cystic fibrosis bronchiectasis accounts for the majority of cases in adults.[4] Risk factors include childhood respiratory infections, environmental exposures like pollution or smoking, and autoimmune diseases such as rheumatoid arthritis.[5]Symptoms typically include a persistent productive cough with copious sputum (often yellow or green), hemoptysis, dyspnea, fatigue, and recurrent exacerbations marked by increased cough and fever.[6] In advanced stages, patients may experience chest pain, wheezing, or digital clubbing, and complications such as pneumonia, lung abscesses, or respiratory failure can arise.[7] Diagnosis relies on clinical history, chest imaging—particularly high-resolution computed tomography (HRCT) revealing bronchial dilation, lack of tapering, or cystic changes—and exclusion of other conditions via pulmonary function tests or bronchoscopy.[8]Management aims to control symptoms, prevent exacerbations, and improve quality of life, as there is no cure for the structural damage.[2] Core treatments include airway clearance therapies (e.g., postural drainage, chest physiotherapy), long-term antibiotics for infection control, mucolytics to thin secretions, and vaccinations against influenza and pneumococcus.[3] For those with underlying causes, targeted therapies like immunoglobulin replacement for immunodeficiencies or CFTR modulators for cystic fibrosis are employed; bronchodilators, inhaled corticosteroids, or surgical resection may be used in select cases.[1] Recent guidelines emphasize multidisciplinary care, including pulmonary rehabilitation, to address the growing global burden, with prevalence estimated at approximately 680 per 100,000 adults as of 2024.[9][10]
Overview
Definition and Classification
Bronchiectasis is a chronic respiratory condition characterized by the irreversible dilatation of the bronchi, resulting from the destruction of the elastic and muscular components of the bronchial walls, which impairs mucociliary clearance and predisposes to recurrent infections.[1] This structural damage distinguishes it from reversible airway narrowing seen in other conditions and leads to a vicious cycle of inflammation and further bronchial remodeling.[11] The condition can occur as a primary disease or secondary to underlying disorders, such as cystic fibrosis, though detailed etiologies are addressed elsewhere.[12]Classifications of bronchiectasis primarily focus on morphological patterns and extent of involvement, aiding in clinical assessment and prognosis. Morphologically, the condition is categorized into three main types based on Reid's seminal 1950 pathological classification: cylindrical (or tubular), featuring uniform, smooth dilatation resembling a tramline; varicose, with irregular, beaded contours due to focal constrictions; and cystic (or saccular), involving severe balloon-like expansions often filled with mucus, representing the most advanced form.[13] These patterns, originally described via bronchography, are now evaluated using high-resolution computed tomography (HRCT).[14] Regarding extent, bronchiectasis is classified as focal if confined to one lobe or segment, typically post-infectious or localized, or diffuse if involving multiple lobes bilaterally, often indicating systemic or genetic underpinnings.[15]Historically, classification systems have evolved from descriptive pathology to multidimensional severity scoring for better prognostic utility. Reid's work in the mid-20th century laid the foundation for morphological typing, correlating gross pathology with bronchographic findings.[16] In the 1990s, the Reiff score introduced a radiological severity metric, assigning points (1-3 per lobe) based on dilatation degree across up to six lobes (maximum score 18), with higher scores indicating greater extent and severity.[17] More recent advancements, endorsed by the European Respiratory Society (ERS), include comprehensive tools like the FACED score (2014) and Bronchiectasis Severity Index (BSI, 2014), which integrate clinical, radiological, and microbiological factors to stratify mortality risk beyond mere morphology.[12] These systems have shifted focus from isolated anatomical features to holistic disease burden assessment.Bronchiectasis must be differentiated from chronic bronchitis, a component of chronic obstructive pulmonary disease defined by productive cough for at least three months in two consecutive years without permanent bronchial dilatation or structural destruction.[18] While both involve chronic airway inflammation, chronic bronchitis lacks the irreversible dilation central to bronchiectasis, often resolving with smoking cessation or management of reversible factors.[19]
Clinical Importance
Bronchiectasis represents a significant global health burden, with a pooled prevalence estimated at 680 per 100,000 adults based on a 2024 meta-analysis of 15 studies encompassing over 437 million individuals.[10] This condition imposes substantial morbidity through recurrent exacerbations, reduced quality of life, and increased risk of respiratory failure, particularly in aging populations where prevalence rises sharply with age. The incidence has been increasing worldwide, driven by improved diagnostic capabilities such as high-resolution computed tomography (HRCT) and demographic shifts toward older age groups, as evidenced by a Chinese cohort study showing a significant rise in urban adult cases from 2013 to 2017.[20]The economic impact of bronchiectasis is profound, primarily due to frequent hospitalizations for acute exacerbations and chronic management needs. A 2023 systematic review of healthcare costs reported annual per-patient expenditures ranging from $3,579 to $82,545 USD in adults, with hospitalizations accounting for the majority of expenses across multiple studies.[21] These costs highlight the strain on healthcare systems, especially in regions with limited access to specialized care.Non-cystic fibrosis bronchiectasis (NCFB) constitutes the majority of cases in adults, often underrecognized and misdiagnosed as chronic obstructive pulmonary disease (COPD), leading to delayed appropriate management. Comprehensive reviews indicate that NCFB accounts for the bulk of bronchiectasis diagnoses beyond childhood, with symptoms like chronic cough and sputum production frequently attributed to COPD in primary care settings.[22] This diagnostic overlap exacerbates the disease burden by postponing interventions that could mitigate progression.Emerging trends since 2020 have further amplified the clinical relevance of bronchiectasis, with post-COVID-19 sequelae contributing to new or worsened cases through mechanisms like persistent inflammation and traction bronchiectasis observed on HRCT imaging.[23] Enhanced HRCT utilization during and after the pandemic has also facilitated earlier detection, underscoring ongoing gaps in awareness and the need for targeted research to address underdiagnosis in non-CF populations. In 2025, the U.S. FDA approved brensocatib (BRINSUPRI), the first targeted therapy for non-cystic fibrosis bronchiectasis, reducing pulmonary exacerbations, alongside updated ERS and CHEST guidelines incorporating these advances.[24][25]
Signs and Symptoms
Respiratory Symptoms
The primary respiratory symptom of bronchiectasis is a chronic productive cough, affecting up to 98% of patients and often present for years. This cough typically involves daily sputum production exceeding 30 mL, which is frequently purulent and results from bacterial colonization in the dilated bronchi.[1] The purulence arises from ongoing inflammation and impaired mucociliary clearance, leading to persistent mucus retention in the airways.[1]Hemoptysis, or coughing up blood, occurs in 56% to 92% of individuals with bronchiectasis and can range from mild streaking of sputum to massive, life-threatening bleeding. It stems from erosion of the bronchial vasculature due to chronic infection and inflammation. While most episodes are minor, severe cases may require urgent intervention.[1][26]Dyspnea, reported in approximately 62% of patients, and wheezing, in about 22%, are common exertional symptoms caused by airflow obstruction from accumulated secretions and bronchial narrowing. These manifestations worsen progressively in advanced disease, sometimes accompanied by digital clubbing, a sign of chronic hypoxemia though uncommon in bronchiectasis.[1][2] Wheezing often presents intermittently, mimicking asthmatic patterns due to reversible airway components.[1]Exacerbations represent acute worsenings of respiratory symptoms, characterized by increased sputum volume and purulence, alongside heightened cough, dyspnea, and wheezing, often triggered by bacterial infections. These episodes, which occur in a majority of patients annually, reflect intensified mucus retention and inflammatory responses in the damaged airways.[27][28]
Systemic Manifestations
Bronchiectasis, as a chronicinflammatorylung condition, often leads to systemic effects beyond the respiratory tract, primarily through sustained inflammation and hypoxemia. Fatigue is a prominent manifestation, resulting from the increased energy demands of labored breathing and the catabolic effects of ongoing inflammation, which elevate resting energy expenditure. Weight loss frequently accompanies this, driven by heightened metabolic needs and reduced caloric intake due to anorexia associated with chronic illness. These symptoms contribute to overall debility and diminished quality of life in affected individuals.[29][1]Digital changes such as finger clubbing and cyanosis arise from chronic hypoxia and vascular alterations in severe cases. Clubbing, characterized by bulbous enlargement of the fingertips, occurs in approximately 2-3% of patients overall but can be observed in up to 50% of pediatric cases or those with advanced disease severity. Cyanosis, a bluish discoloration of the skin and mucous membranes, reflects inadequate oxygenation and is more common in advanced bronchiectasis with significant ventilatory impairment.[1][30]Secondary systemic complications further compound the burden of bronchiectasis. Malnutrition develops from persistent anorexia and malabsorption secondary to chronic inflammation, exacerbating weight loss and frailty. Anemia of chronic disease is common, stemming from inflammatory cytokines that suppress erythropoiesis and iron utilization. Osteoporosis is prevalent, particularly in males with low body mass index and severe bronchial involvement, worsened by immobility from dyspnea and potential use of corticosteroids in management.[31][32][33]The psychological toll of bronchiectasis is substantial, with anxiety and depression reported in 20% to 65% of patients across studies, attributable to the unrelenting burden of symptoms, frequent hospitalizations, and lifestyle restrictions imposed by the chronic illness. These mental health issues can perpetuate a cycle of reduced adherence to therapy and worsened physical outcomes.[34]
Causes and Risk Factors
Acquired Causes
Acquired causes of bronchiectasis encompass a range of environmental, infectious, and systemic factors that lead to bronchial damage in individuals without inherent genetic predispositions. These etiologies often involve recurrent or severe insults to the airways, resulting in irreversible dilatation and impaired mucociliary clearance. Post-infectious processes represent the predominant acquired mechanism, accounting for approximately 30-40% of cases globally, though prevalence varies by region and population.[35] Other contributors include mechanical obstructions, immunodeficiencies, toxic exposures, and autoimmune conditions, each predisposing the lungs to chronic inflammation and infection.Post-infectious bronchiectasis is the most common acquired form, arising from severe or repeated respiratory infections that damage bronchial walls and promote persistent microbial colonization. In childhood, infections such as measles or pertussis can initiate this process, while in adults, bacterial pneumonia—particularly from pathogens like Pseudomonas aeruginosa or Haemophilus influenzae—or nontuberculous mycobacterial infections are frequent triggers.[36] Studies indicate that post-infectious etiologies comprise 19-40% of bronchiectasis cases, with higher rates in regions where tuberculosis remains endemic, such as parts of Asia.[37] These infections disrupt normal airway defenses, leading to a cycle of inflammation and structural remodeling that culminates in bronchiectasis.Airway obstruction contributes to acquired bronchiectasis by causing distal bronchial collapse, mucus stasis, and secondary infections. Common culprits include aspirated foreign bodies, endobronchial tumors, or extrinsic compression from enlarged lymph nodes due to malignancy or granulomatous disease.[1] This mechanical impediment impairs ventilation and clearance, fostering atelectasis and recurrent pneumonia in affected lung segments. While less prevalent than post-infectious causes, obstruction accounts for a notable subset of cases, particularly in pediatric or oncologic populations, and early removal of the obstructing lesion can mitigate progression.[38]Acquired immunodeficiencies heighten susceptibility to recurrent pulmonary infections, thereby promoting bronchiectasis through chronic airway insult. Conditions such as HIV/AIDS or secondary hypogammaglobulinemia—often linked to medications, malignancies, or protein-losing enteropathies—compromise humoral immunity and mucociliary function.[39] For instance, in HIV patients, opportunistic infections exacerbate bronchial damage, with bronchiectasis prevalence rising as CD4 counts decline. Immunoglobulin replacement therapy in hypogammaglobulinemia cases has shown potential to reduce infection frequency and slow structural lung changes. Secondary immunodeficiencies underlie about 5-12% of bronchiectasis etiologies in adults.[40][41]Toxic exposures represent another key acquired pathway, where irritants directly injure bronchial epithelium or indirectly worsen infection susceptibility. Chronic aspiration, often associated with gastroesophageal reflux disease (GERD) or dysphagia, introduces gastric contents into the airways, causing chemical pneumonitis and subsequent fibrosis.[42] Inhalational injuries from smoke, ammonia, or other chemicals can induce acute bronchiolitis and long-term dilatation, as seen in cases of hydrocarbon aspiration or industrial accidents. Cigarette smoking acts as a disease modifier, accelerating severity by impairing ciliary function and increasing oxidative stress, with smokers exhibiting higher exacerbation rates and worse lung function in bronchiectasis cohorts.[43][44][45]Autoimmune diseases, particularly rheumatoid arthritis (RA), are significant acquired contributors, with pulmonary involvement manifesting as vasculitis or immune-mediated bronchial destruction. Up to 20% of RA patients develop bronchiectasis, often independently of rheumatoid nodules or interstitial lung disease, due to systemic inflammation targeting airway walls.[46] Prevalence estimates from high-resolution CT studies range from 15-29%, with risk factors including longer disease duration and seropositivity for rheumatoid factor. Other autoimmune conditions, such as Sjögren's syndrome, may similarly predispose through lymphocytic infiltration, though RA remains the most strongly associated. Disease-modifying antirheumatic drugs can influence outcomes, but screening for bronchiectasis is recommended in at-risk RA populations.[47]
Genetic and Congenital Causes
Bronchiectasis can arise from genetic mutations that impair airway clearance or structural integrity, with cystic fibrosis representing the most prominent monogenic cause. Caused by biallelic mutations in the CFTR gene on chromosome 7, cystic fibrosis leads to defective chloride transport, resulting in viscous mucus accumulation in the airways that predisposes to recurrent infections and progressive bronchial dilation. Genotype-phenotype correlations are well-established; for instance, patients with at least one ΔF508 mutation often exhibit severe pulmonary involvement, including early-onset bronchiectasis, while milder alleles like R117H may present with later, less aggressive disease. In cohorts of bronchiectasis patients, cystic fibrosis accounts for approximately 3-10% of cases in adults, though this proportion rises to 10-15% in pediatric populations where screening is routine.[48] Augmentation therapies targeting CFTR function, such as ivacaftor for specific mutations, can mitigate mucus-related damage and slow bronchiectasis progression.Primary ciliary dyskinesia (PCD), another key genetic etiology, stems from autosomal recessive mutations disrupting motile cilia structure and function, thereby abolishing effective mucociliary clearance and fostering chronic airway inflammation and bronchiectasis.[49] Common defects involve dynein arms, as seen in mutations of DNAH5 (encoding an outer dynein arm heavy chain) or DNAI1, which together account for 15-30% of PCD cases; more recent identifications include CCDC39 and CCDC40 variants affecting inner dynein arms, discovered around 2010 but with expanded clinical correlations post-2015 through next-generation sequencing.[50] Approximately 50% of PCD patients develop situs inversus, defining Kartagener syndrome, a subtype where bronchiectasis often manifests in the upper lobes due to impaired embryonic nodal cilia.[51] PCD underlies 1-5% of non-cystic fibrosis bronchiectasis in adults, with whole-genome sequencing revealing underdiagnosis in up to 20% of unexplained cases through detection of biallelic variants in over 40 ciliopathy genes.[52]Additional genetic conditions contribute less frequently but distinctly to bronchiectasis pathogenesis. Alpha-1 antitrypsin deficiency (AATD), resulting from SERPINA1 gene mutations (notably PiZ and PiS alleles), diminishes protease inhibition in the lung, promoting unchecked elastase activity that erodes bronchial walls and induces dilatation, observed in 25-30% of severe AATD patients.[53] In bronchiectasis cohorts, AATD prevalence ranges from 1-2%, with augmentation therapy using purified alpha-1 antitrypsin potentially stabilizing lung function in affected individuals.[54]Marfan syndrome, caused by FBN1 mutations disrupting connective tissue, rarely associates with bronchiectasis (prevalence <5% in Marfan cohorts), likely via weakened bronchial cartilage or chest wall deformities impairing ventilation.[55]Congenital malformations represent developmental origins of bronchiectasis, independent of ciliary or mucus defects. Mounier-Kuhn syndrome, or congenital tracheobronchomegaly, features atrophy of elastic and smooth muscle in the trachea and proximal bronchi due to unknown genetic factors, leading to flaccid airways prone to collapse and secondary infections with bronchiectasis in 70-90% of cases. Williams-Campbell syndrome involves deficient cartilage in fourth- to sixth-order bronchi, a rare autosomal recessive or sporadic condition causing expiratory collapse and cystic bronchiectasis predominantly in the mid-lung zones.[56]
Pathophysiology
Mechanisms of Bronchial Damage
Bronchiectasis is characterized by a self-perpetuating "vicious cycle" of airway damage, first proposed by Cole in 1986, wherein initial insults such as infection or inflammation impair mucociliary clearance, leading to recurrent bacterial colonization and persistent neutrophilic inflammation that further exacerbates bronchial dilation and tissue destruction.[13] This model has been updated in recent years to a "vicious vortex" framework that emphasizes four interconnected drivers: chronic infection, inflammation, impaired mucociliary clearance, and structural lung damage.[57] This cycle involves the release of neutrophil elastase (NE), a serine protease from activated neutrophils, which degrades elastin in the airway wall, compromising structural integrity and promoting irreversible dilatation.[58] Elevated sputum NE levels in stable bronchiectasis patients correlate with disease severity, underscoring its role in perpetuating the inflammatory loop.[59]Airway wall remodeling in bronchiectasis manifests as profound structural alterations, including loss of ciliated epithelium, squamous metaplasia, and hypertrophy of airway smooth muscle, which collectively impair normal airway function and contribute to dilation.[60] The reduction in ciliated cells disrupts mucociliary transport, while squamous metaplasia replaces functional epithelium with stratified squamous cells, further hindering clearance and fostering a pro-inflammatory environment.[61] Smooth muscle hypertrophy thickens the airway wall, potentially exacerbating obstruction and remodeling through mechanical stress and cytokine-mediated pathways.[62]Mucus hypersecretion arises from goblet cell hyperplasia and a diminished periciliary layer, leading to viscous mucus accumulation that stagnates in dilated bronchi and amplifies infection risk.[63] This process is driven by elevated proinflammatory cytokines such as interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α), which promote goblet cell differentiation and mucus production while recruiting additional neutrophils.[59] Sputum levels of IL-8 and TNF-α are markedly increased in bronchiectasis, correlating with neutrophil influx and hypersecretion severity.[64]Vascular changes in bronchiectasis include hypertrophy of bronchial arteries, a compensatory response to chronic hypoxia and inflammation that increases blood flow to damaged areas but heightens the risk of hemoptysis.[65] Dilated bronchial arteries, often exceeding 2 mm in diameter, become fragile and prone to rupture, particularly in severe disease, making them a primary source of life-threatening bleeding.[66] This neovascularization is linked to ongoing tissue repair but contributes to the overall pathology by promoting edema and further airway instability.[67]
Inflammatory and Infectious Processes
Chronic infection plays a central role in the progression of bronchiectasis, with Pseudomonas aeruginosa being a predominant pathogen responsible for 20-40% of bacterial infections.[68] This bacterium forms biofilms within the dilated airways, which are facilitated by bronchial structural damage, enhancing its persistence and resistance to host defenses and antibiotics.[69] Biofilm formation involves quorum sensing mechanisms, where P. aeruginosa coordinates gene expression through signaling molecules like acyl-homoserine lactones, promoting the production of extracellular polymeric substances that shield bacterial communities.[70]The host immune response in bronchiectasis is characterized by dysregulated inflammation, including exaggerated Th2-mediated pathways that contribute to eosinophilic infiltration alongside dominant neutrophilic responses.[71] Alveolar macrophages exhibit impaired phagocytosis, particularly against common respiratory pathogens like nontypeable Haemophilus influenzae, leading to reduced clearance of apoptotic cells and bacteria, which perpetuates inflammation and microbial colonization.[72] Emerging research as of 2025 explores targeted therapies for neutrophil dysfunction, such as dipeptidyl peptidase 1 (DPP-1) inhibitors, to interrupt these inflammatory pathways.[73]Biomarkers of disease activity include elevated sputum neutrophil counts, often exceeding thresholds indicative of active inflammation, and high levels of free DNA derived from neutrophil extracellular traps, both correlating with exacerbation risk and lung function decline.[74] These markers reflect the intensity of ongoing neutrophilic inflammation and can guide monitoring of inflammatory burden.Recent post-2022 research highlights microbiome dysbiosis in bronchiectasis, characterized by reduced microbial diversity and dominance of pathogens like P. aeruginosa, which is strongly linked to increased exacerbation frequency and poorer clinical outcomes.[75] This dysbiosis disrupts ecological balance in the airways, fostering chronic infection cycles that amplify inflammatory processes.
Diagnosis
Clinical Evaluation
The clinical evaluation of suspected bronchiectasis begins with a detailed history to identify characteristic features and potential etiologies. Patients typically report a chronic cough lasting months to years, often productive of daily sputum that may be mucopurulent or purulent, with volumes exceeding 30 mL per day in moderate to severe cases.[76] Inquiry should focus on the frequency and severity of exacerbations, defined as worsening respiratory symptoms requiring antibiotics or hospitalization, as recurrent episodes (e.g., two or more per year) are common and inform disease severity.[1] A family history of cystic fibrosis (CF) or primary ciliary dyskinesia (PCD) is crucial to screen for genetic causes, prompting targeted testing if present.[77]Physical examination may reveal signs of chronic airway disease, though findings can be normal in mild cases. Auscultation frequently detects crackles, present in approximately 75% of patients and often bibasilar, reflecting mucus accumulation and bronchial dilation; wheezes occur in about 22% due to airflow limitation.[1] Digital clubbing is observed in variable degrees, particularly in advanced disease or with hypoxemia, while rhonchi may indicate underlying airway obstruction from causes like foreign body aspiration or tumors.[78] Additional findings, such as signs of systemic involvement (e.g., weight loss or fatigue), help assess overall impact.Risk stratification during evaluation employs validated scoring tools like the Bronchiectasis Severity Index (BSI), which integrates clinical variables including age (>70 years scoring higher risk), forced expiratory volume in 1 second (FEV1 <30% predicted indicating severe impairment), and history of exacerbations or hospitalizations to predict mortality, future exacerbations, and healthcare needs.[79] The BSI categorizes patients into low (0-4 points), intermediate (5-8 points), or high (≥9 points) risk groups, guiding management intensity without requiring imaging.Differential diagnosis emphasizes distinguishing bronchiectasis from conditions like asthma or chronic obstructive pulmonary disease (COPD), where persistent daily sputum production and recurrent infections predominate, unlike the episodic symptoms and reversible airflow obstruction in asthma or fixed obstruction in COPD.[80] Symptoms such as chronic cough and sputum production often prompt this evaluation.[76]
Imaging and Laboratory Tests
High-resolution computed tomography (HRCT) of the chest serves as the gold standard for diagnosing bronchiectasis, providing detailed visualization of bronchial abnormalities that confirm the condition.[81] Key radiographic signs include bronchial dilatation, where the internal diameter of the bronchus exceeds that of the adjacent pulmonary artery (bronchoarterial ratio >1), often manifesting as the classic signet ring sign on axial images; lack of normal bronchial tapering toward the periphery; and bronchial wall thickening, typically exceeding 1.5 mm in adults.[82][83] These features are most evident in the lower lobes and allow differentiation from other airway diseases, with HRCT sensitivity approaching 95% for detecting bronchiectasis when performed with thin-section slices (1-2 mm).[84]To assess disease severity and extent, the Bhalla scoring system is widely used, originally developed for cystic fibrosis but adapted for non-cystic fibrosis bronchiectasis; it evaluates multiple parameters including the degree of bronchiectasis, bronchial wall thickening, mucus plugging, and associated changes like sacculation or generations of bronchial involvement, yielding a total score from 3 to 25, where lower scores indicate more severe structural damage.[85][86]Laboratory tests support the diagnosis by identifying underlying etiologies and infectious contributors. Sputum culture and microscopy are essential to detect common pathogens such as Haemophilus influenzae and Pseudomonas aeruginosa, guiding targeted antimicrobial therapy and revealing chronic colonization patterns in up to 70% of cases.[87][88] For suspected cystic fibrosis as a cause, quantitative sweat chloride testing remains the gold standard, with levels >60 mmol/L diagnostic in most contexts, often confirmed by genetic analysis of CFTR mutations.[81]Serum immunoglobulin levels (IgG, IgA, IgM, and subclasses) are routinely measured to screen for immunodeficiencies, as hypogammaglobulinemia underlies approximately 10-15% of non-cystic fibrosis bronchiectasis cases.[89]Pulmonary function tests typically reveal an obstructive ventilatory defect, characterized by a reduced forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC <70%), reflecting airflow limitation due to bronchial distortion.[90] Hyperinflation is common, evidenced by elevated residual volume (>120% predicted) and total lung capacity (>120% predicted), indicating air trapping from impaired mucociliary clearance.[91]In cases of focal or localized bronchiectasis, flexible bronchoscopy may be employed for direct visualization, biopsy, or targeted cultures to exclude endobronchial obstructions like tumors or foreign bodies, particularly when HRCT suggests asymmetry without an evident infectious trigger.[81]Recent advances in imaging incorporate artificial intelligence (AI) enhancements to HRCT for earlier detection, such as automated quantification of bronchiectasis severity via airway-to-artery ratios and texture analysis, improving sensitivity for subclinical changes in at-risk populations like those with COPD.[92][93]
Prevention
Primary Prevention Strategies
Primary prevention of bronchiectasis focuses on averting the initial onset by targeting modifiable risk factors, particularly in vulnerable populations such as children and individuals with potential predispositions to severe respiratory infections. Vaccination plays a central role in this strategy, as post-infectious damage from pathogens like Streptococcus pneumoniae, influenza virus, and Bordetella pertussis is a leading acquired cause. Routine immunization with pneumococcal conjugate vaccines (PCV15, PCV20, or PCV21), annual influenza vaccines, and the pertussis component of DTaP/Tdap has contributed to reducing the incidence of severe lower respiratory infections that can lead to bronchiectasis by reducing severe lower respiratory infections, potentially mitigating risks for its development.[94] For instance, widespread PCV implementation has lowered invasive pneumococcal disease rates by up to 90% in vaccinated children, indirectly mitigating risks for chronic lung sequelae.[95][96][97]Environmental controls are essential for minimizing exposure to irritants that exacerbate airway vulnerability, especially in children where indoor air pollution from biomass fuels or secondhand smoke heightens infection susceptibility. Public health programs promoting smoking cessation among adults and prohibiting tobacco exposure around children can significantly lower bronchiectasis risk, as active and passive smoking impairs mucociliary clearance and is associated with a small increased risk (adjusted hazard ratio 1.06–1.12 for current smokers) of non-cystic fibrosis bronchiectasis.[98] Similarly, interventions to reduce indoor pollutants—such as improved ventilation, use of clean cooking fuels, and air filtration—have been shown to decrease respiratory symptoms and infection frequency in at-risk households, with studies reporting up to 50% reductions in particulate matter exposure leading to fewer acute events. These measures are particularly impactful in low-resource settings where household air pollution affects approximately 2.6 billion people globally as of 2023.[99][100][101]Early intervention for aspiration risks in infants, often linked to gastroesophageal reflux disease (GERD), is critical to prevent recurrent microaspiration that damages airways. Non-pharmacologic strategies like upright positioning after feeds, thickened formula, and smaller, more frequent meals can help reduce reflux episodes in affected infants, thereby lowering the incidence of aspiration pneumonia and subsequent bronchiectasis development. In cases of suspected GERD, timely evaluation and management—guided by pediatric gastroenterology guidelines—help avert chronic lung injury, with conservative therapies often resolving symptoms in many infants without progression to respiratory complications.[102][103]Public health efforts also include screening for underlying immunodeficiencies in children presenting with recurrent respiratory infections, enabling early immunoglobulin replacement or antimicrobial prophylaxis to halt progression to bronchiectasis. For example, newborn screening for severe combined immunodeficiency (SCID) has increased early diagnosis rates, enabling early intervention to prevent complications such as bronchiectasis through timely intervention. Targeted testing for antibody deficiencies in those with two or more severe infections per year—such as measuring IgG, IgA, and IgM levels—facilitates proactive care, as untreated primary immunodeficiencies account for 10-20% of pediatric bronchiectasis cases.[104][105]
Secondary Prevention Measures
Secondary prevention in bronchiectasis focuses on strategies to mitigate disease progression and reduce the frequency of exacerbations in individuals already diagnosed with the condition. A key component is infection prophylaxis through long-term macrolideantibiotic therapy, particularly for patients experiencing frequent exacerbations (defined as three or more per year). Azithromycin, administered at a dose of 250 mg three times per week, has been shown to significantly decrease the rate of pulmonary exacerbations by approximately 44% compared to placebo, based on moderate-certainty evidence from randomized controlled trials.[106] This regimen is recommended by major guidelines for non-cystic fibrosis bronchiectasis patients without Pseudomonas aeruginosainfection, with treatment typically continued for at least 6 to 12 months and reassessed based on response.[107][108] Long-term use requires monitoring for side effects such as gastrointestinal upset, hearing changes, and antimicrobial resistance, with dose adjustments (e.g., to 500 mg three times weekly) considered if tolerated.[109]Education on airway hygiene is essential for long-term control, emphasizing techniques that promote mucus clearance and minimize bronchial stasis to prevent recurrent infections. Daily postural drainage, involving specific body positions to use gravity-assisted clearance combined with percussion or vibration, is a cornerstone intervention taught to patients and caregivers. Guidelines strongly endorse regular airway clearance techniques for all bronchiectasis patients, as they improve sputum expectoration, reduce infection risk, and enhance quality of life without significant adverse effects.[107][108] Patient adherence is supported through structured training programs, often integrated with devices like oscillating positive expiratory pressure masks for added efficacy during stable periods.Managing associated comorbidities plays a critical role in secondary prevention by addressing factors that exacerbate bronchial inflammation or promote aspiration. Treatment of chronic rhinosinusitis, which affects up to 60% of bronchiectasis patients and facilitates post-nasal drip of pathogens, involves nasal irrigation, topical corticosteroids, and antibiotics as needed to reduce lower airway colonization. Similarly, optimizing gastroesophageal reflux disease (GERD) management with proton pump inhibitors and lifestyle modifications (e.g., elevated head of bed) minimizes acid aspiration, a known trigger for exacerbations in susceptible individuals.[107] Routine screening and multidisciplinary care for these conditions are advised to interrupt vicious cycles of inflammation and infection.Ongoing monitoring is vital to detect early progression and adjust preventive measures accordingly. Annual reassessment using the Bronchiectasis Severity Index (BSI), which incorporates clinical, radiological, and microbiological parameters, helps stratify risk and guide therapy intensification. High-resolution computed tomography (HRCT) scans may be performed annually or as indicated in moderate-to-severe cases to evaluate structural changes, though radiation exposure limits routine use; alternatives include serial spirometry and symptom tracking.[107] This proactive approach enables timely interventions to preserve lung function and avert complications such as respiratory failure.
Management and Treatment
Airway Clearance Techniques
Airway clearance techniques (ACTs) form a cornerstone of non-pharmacological management for bronchiectasis, aiming to mobilize and remove retained secretions from the airways to reduce infection risk, improve lung function, and enhance quality of life. These techniques address the viscous mucus hypersecretion characteristic of the condition, which impairs mucociliary clearance and perpetuates a cycle of inflammation and damage. Regular use of ACTs has been shown to increase sputum expectoration and decrease exacerbation frequency in stable patients.[110][111]Physiotherapy-based ACTs, such as the active cycle of breathing technique (ACBT), involve a sequence of breathing control, thoracic expansion exercises, and forced expiration to facilitate mucus mobilization without mechanical aids. ACBT is effective in increasing expectorated sputum volume, reducing secretion viscoelasticity, and alleviating symptoms like dyspnea in adults with bronchiectasis. It outperforms techniques like timed incentive spirometry in single sessions by enhancing sputum clearance during treatment. Positive expiratory pressure (PEP) therapy, another physiotherapy approach, uses devices to generate resistance during exhalation, preventing airway collapse and promoting collateral ventilation to loosen secretions. PEP devices have demonstrated benefits in improving cough efficacy and mucus expectoration compared to no treatment, with studies showing significant increases in sputum volume post-session.[112][113][114]Specialized devices enhance the efficacy of ACTs for patients with limited mobility or severe disease. Oscillatory PEP devices, such as the Flutter valve, combine PEP with high-frequency oscillations to vibrate and shear mucus from airway walls, improving secretion transport more effectively than standard PEP in some cases. These handheld tools are portable and user-friendly, leading to better sputum clearance and quality-of-life scores in stable non-cystic fibrosis bronchiectasis. High-frequency chest wall oscillation (HFCWO), delivered via an inflatable vest connected to a generator, applies external vibrations to the thorax at frequencies of 5-25 Hz, dislodging mucus and aiding its expulsion through coughing. HFCWO has been associated with reduced hospitalizations, antibiotic use, and improved self-reported outcomes in real-world bronchiectasis cohorts.[114][115][116]Postural drainage leverages gravity to drain secretions from specific lung lobes by positioning the patient with the affected area uppermost, often combined with percussion or vibration for enhanced effect. Positions are tailored to bronchiectasis distribution, such as side-lying with the upper lobe elevated for apical involvement or prone with hips raised for basal segments; the knee-chest position is particularly effective for lower lobe clearance. This technique is simple, cost-free, and suitable for home use, though it requires instruction to avoid discomfort.[117][118]Patient education is essential for optimizing ACT adherence, which remains low at approximately 41% for airway clearance in bronchiectasis, influenced by factors like perceived burden and lack of tailored training. Structured programs emphasizing technique demonstration, self-monitoring of sputum volume, and integration into daily routines improve compliance and long-term outcomes, with video consultations showing high satisfaction and effectiveness in remote settings. Adherence is higher among those with more severe symptoms, underscoring the need for personalized education to empower self-management.[119][120][121]
Pharmacological Therapies
Pharmacological therapies for bronchiectasis primarily target chronic airway infection, inflammation, mucus hypersecretion, and airflow obstruction to reduce exacerbations, improve lung function, and enhance quality of life.[122] Antibiotics form the cornerstone, with choices guided by sputummicrobiology and exacerbation frequency.[123]Long-term antibiotic therapy is recommended for patients with frequent exacerbations (≥3 per year) or chronic bacterial colonization, particularly Pseudomonas aeruginosa. Inhaled antibiotics, such as tobramycin inhalation solution (300 mg twice daily for 28 days on/off cycles), reduce bacterial load in sputum and have shown a 30% reduction in exacerbations in patients with chronic P. aeruginosa infection, based on pooled data from randomized trials.[124] The RESPIRE trials demonstrated sustained reductions in Pseudomonas density without significant overall exacerbation benefit in broader non-CF bronchiectasis populations, but guidelines endorse their use in pathogen-specific cases due to improved symptom control and fewer hospitalizations.[125] For acute exacerbations requiring hospitalization, intravenous antibiotics like ceftazidime or piperacillin-tazobactam are standard, targeting isolated pathogens and typically administered for 10-14 days to resolve symptoms and prevent progression.[123]Anti-inflammatory agents address persistent airway inflammation beyond infection control. Low-dose macrolides, such as erythromycin (250 mg daily), exert immunomodulatory effects and are recommended for adults with ≥2 exacerbations per year; the BLESS trial reported a 35% reduction in exacerbation frequency over 12 months compared to placebo, alongside improved quality of life scores.[126] Emerging biologics target eosinophilic subsets; mepolizumab (anti-IL-5 monoclonal antibody, 100 mg subcutaneously every 4 weeks) has shown symptom improvement and reduced infectious exacerbations in small cohorts of patients with severe eosinophilicasthma and comorbid bronchiectasis.[127] Brensocatib, a dipeptidyl peptidase 1 inhibitor (10-25 mg daily oral), inhibits neutrophil serine proteases and reduced pulmonary exacerbations by 18.3% (25 mg dose) versus placebo in the phase 3 ASPEN trial (n=1681), with additional slowing of lungfunction decline; it received FDA approval in 2025 as the first specific therapy for non-CF bronchiectasis.[128]Bronchodilators and mucoactive agents alleviate airflow limitation and facilitate clearance. Inhaled short-acting beta-agonists (e.g., salbutamol 2.5-5 mg nebulized) or long-acting muscarinic antagonists (e.g., tiotropium 18 mcg daily) are used in patients with reversible obstruction (≥12% FEV1 improvement post-bronchodilator), improving exercise tolerance per ERS guidelines.[122] Nebulized hypertonic saline (7%, 4 mL twice daily) hydrates airway surfaces and enhances mucociliary clearance; older randomized trials report 10-15% absolute improvements in FEV1, but a large phase 3 trial in 2025 found no significant reduction in exacerbation rates over 52 weeks in non-CF bronchiectasis.[129][130]In bronchiectasis associated with cystic fibrosis (CF), CFTR modulators address underlying ion channel defects in patients with eligible mutations. Elexacaftor-tezacaftor-ivacaftor (150/100/75 mg oral twice daily, known as Trikafta) improves CFTR function, leading to 10-14% mean FEV1 gains and 63% reduction in exacerbations in CF populations; recent 2025 data extend benefits to non-CF bronchiectasis with amenable CFTR variants (e.g., F508del), showing enhanced lung function, symptom relief, and fewer annual exacerbations in small cohorts.[131] Pathogen-specific targeting complements these therapies, as detailed in inflammatory processes.[111]
Surgical and Interventional Options
Surgical resection remains a cornerstone for managing localized bronchiectasis refractory to conservative measures, particularly in cases involving recurrent infections or significant hemoptysis. Lobectomy, which involves removal of the affected lung lobe, is the preferred procedure when disease is confined to one or two lobes, allowing preservation of functional lungtissue. Complete resection of bronchiectatic areas achieves symptom relief or cure in 70-80% of patients, with lower rates of recurrence and improved quality of life compared to incomplete resections.[132] Operative mortality is low (0-2%), though morbidity from complications such as prolonged air leak or infection occurs in 10-20% of cases, emphasizing the need for careful patient selection based on preoperative imaging and pulmonary function.[133]For patients with end-stage diffuse bronchiectasis and advanced respiratory failure, lung transplantation offers a definitive treatment option after failure of maximal medical therapy. Bilateral lung transplantation is typically performed, with indications including severe airflow obstruction, frequent exacerbations, and hypoxemia. Five-year post-transplant survival in adults with non-cystic fibrosis bronchiectasis reaches approximately 61%, comparable to outcomes in other chronic lung diseases, though early mortality from sepsis remains a concern.[134] Long-term success depends on multidisciplinary care to manage rejection and infections, with many recipients experiencing substantial improvements in exercise capacity and quality of life.30064-6/fulltext)Bronchoscopic therapies provide less invasive alternatives for targeted intervention in bronchiectasis, especially for localized hyperinflation or structural abnormalities contributing to symptoms. Endobronchial valve placement involves deploying one-way valves to isolate hyperinflated lung segments, promoting atelectasis and redistribution of ventilation, while coils compress diseased tissue to achieve volume reduction. These approaches are suitable for patients with comorbid emphysema or heterogeneous disease distribution. Recent studies from 2023-2025 demonstrate that endobronchial valves can reduce exacerbation frequency by up to 50% in selected cases with complete lobar occlusion, alongside improvements in dyspnea and lungfunction.[135] Complications such as pneumothorax (up to 25%) or valve migration are manageable bronchoscopically, making this a bridge to transplantation in advanced disease.[136]Palliative interventional procedures are crucial for life-threatening complications like massive hemoptysis, which arises from hypertrophied bronchial arteries in bronchiectasis. Bronchial artery embolization (BAE) entails catheter-directed occlusion of aberrant vessels using particles or coils, achieving immediate hemostasis in over 90% of cases. For bronchiectasis-related hemoptysis, BAE controls massive bleeding effectively with low procedural mortality (<1%), though recurrence occurs in 10-30% within the first year, often necessitating repeat interventions.[137] This technique is preferred over surgery in unstable patients due to its minimally invasive nature and rapid recovery.
Prognosis and Complications
Factors Affecting Outcomes
Several validated prognostic scores assist in predicting mortality and disease progression in patients with bronchiectasis, enabling riskstratification for personalized management. The FACED score, which incorporates forced expiratory volume in 1 second (FEV1), age, chronic Pseudomonas aeruginosa colonization, radiological extension of disease, and dyspnea severity, stratifies patients into mild, moderate, and severe risk categories with 5-year mortality rates of approximately 3.7%, 20.7%, and 48.5%, respectively.[139] Similarly, the Bronchiectasis Severity Index (BSI) integrates nine factors including age, FEV1, dyspnea, sputum purulence, exacerbations, body mass index, Pseudomonas colonization, hospitalization history, and lung function to predict 1-year mortality (ranging from 0-2.8% in mild cases to higher rates in severe disease) and overall 5-year mortality risks of 3-40%.[140][141]Modifiable factors significantly influence outcomes, with chronic isolation of Pseudomonas aeruginosa approximately doubling the risk of hospitalization for acute exacerbations compared to non-colonized patients.[142]Smoking exacerbates disease progression by promoting airway inflammation.[143]Demographic characteristics also play a key role, as patients over 65 years exhibit roughly twice the mortality risk compared to younger adults, driven by comorbidities and reduced physiological reserve.[144]Long-term survival has improved markedly in contemporary cohorts, reflecting advances in care. Co-infection with nontuberculous mycobacteria (NTM) is associated with poorer prognosis, including higher mortality and exacerbation rates, affecting up to 20% of patients in some cohorts as of 2023.[145]
Common Complications
One of the most common complications of bronchiectasis is recurrent pneumonia, which arises from the structural damage to the airways that impairs mucociliary clearance and fosters persistent bacterial colonization, facilitating repeated infectious episodes that manifest as lobar consolidation and contribute to progressive pulmonary fibrosis. This vulnerability leads to frequent exacerbations requiring antibiotic therapy, with patients often experiencing multiple episodes annually due to the cycle of inflammation and infection.[1][95][27]Hemoptysis and lung abscess represent significant pulmonary complications, where hemoptysis results from the erosion of hypertrophied bronchial arteries and mucosal vessels amid chronic inflammation and infection within the dilated bronchi. Massive hemoptysis, defined as life-threatening bleeding exceeding 100-600 mL in 24 hours, affects approximately 16% of patients with bronchiectasis and can lead to acute airway compromise or exsanguination if untreated. Lung abscess develops through localized tissue necrosis from severe, untreated infections, often involving anaerobicbacteria, and is recognized by symptoms of foul-smelling sputum, fever, and imaging showing cavitary lesions.[1][146][147]Respiratory failure is a severe end-stage complication in advanced bronchiectasis, driven by progressive airflow obstruction, ventilation-perfusion mismatch, and chronic hypoxemia that culminates in hypercapnic or hypoxemic failure requiring mechanical ventilation. This often coexists with cor pulmonale, where sustained pulmonary hypertension from hypoxic vasoconstriction and vascular remodeling imposes right ventricular strain, leading to heart failure; recognition involves echocardiography showing right ventricular hypertrophy and dilation alongside clinical signs of peripheral edema and exertional dyspnea.[1][148][149]Extrapulmonary complications include secondary amyloidosis, which emerges from prolonged systemic inflammation depositing amyloid A protein in organs like the kidneys, resulting in nephrotic syndrome with proteinuria and renal dysfunction; though now less common due to improved management, it affects a subset of patients with longstanding, severe disease. Recent observations highlight rising post-viral complications, such as organizing pneumonia following infections like COVID-19, characterized by intra-alveolar fibroblastic plugs and patchy consolidation on imaging, particularly in those with preexisting bronchial vulnerability.[1][150][151]
Epidemiology
Global Prevalence and Distribution
Bronchiectasis exhibits significant global variability in prevalence, with estimates ranging from 50 to 1000 cases per 100,000 individuals due to differences in diagnostic practices and reporting.[152] In high-income regions such as Europe and Australia, reported prevalence is higher, typically between 67 and 566 per 100,000, reflecting improved access to high-resolution computed tomography (HRCT) imaging; for instance, rates reach 566 per 100,000 in the United Kingdom, while lower figures like 67 per 100,000 are noted in Germany.[153] In contrast, prevalence appears underreported in low- and middle-income regions like parts of Asia and Africa, with estimates varying widely (e.g., below 50 per 100,000 in some areas to over 400 per 100,000 in others in Asia), attributed to limited diagnostic resources and underrecognition of the condition despite high burdens from post-infectious etiologies such as tuberculosis.[154] A 2024 meta-analysis pooling data from multiple countries estimated a global adult prevalence of 680 per 100,000 (95% CI: 634–727), underscoring the disease's commonality but highlighting regional disparities.[10] A 2025 narrative review notes declining prevalence in certain high-income cohorts born after the 1970s (e.g., 11.0 per 1,000 born in the 1980s in the US), while pediatric registries highlight increasing recognition in children globally.[155]Incidence rates for bronchiectasis also vary geographically, ranging from 8 to 29 new cases per 100,000 adults annually, with higher figures in North America (29 per 100,000 in the United States) and more stable but lower rates in Asia (around 19 per 100,000 in Hong Kong).[156][157] Overall, incidence has been increasing worldwide at approximately 2-3% per year, driven by aging populations, better detection through imaging, and rising awareness, though rates in the United States have shown steeper annual growth of about 8%.[158][159]Geographic variations are pronounced in indigenous populations, where prevalence is substantially elevated due to factors like recurrent childhood infections and environmental exposures; for example, Alaska Native children in the Yukon Kuskokwim Delta experience rates up to four times higher than the general population, with approximately 1 in 63 affected.[160] Similar disparities occur among Australian Aboriginal and New Zealand Māori communities, where bronchiectasis is more common and presents earlier in life.[161]Recent trends indicate a post-2020 surge in bronchiectasis cases associated with long COVID, with approximately 16.8% (95% CI: 9.1–26.1%) of COVID-19 survivors showing bronchiectasis on post-infection imaging, contributing to the global rise in non-cystic fibrosis bronchiectasis diagnoses.[162]
Risk Factors in Populations
Bronchiectasis predominantly affects older adults, with peak onset occurring between the ages of 50 and 70 years, as evidenced by cohort studies showing a median age of 67 years at diagnosis. Prevalence rates rise substantially with advancing age, from approximately 7 per 100,000 in individuals aged 18–34 years to over 800 per 100,000 in those aged 75 years and older, reflecting cumulative exposures to respiratory insults over time.[163][156][164] In non-cystic fibrosis cases, there is a slight female predominance, with a female-to-male ratio of about 1.5:1; prevalence estimates indicate 566 cases per 100,000 women compared to 485 per 100,000 men in certain populations, potentially linked to factors such as longer endogenous estrogen exposure or differences in immune responses to infections.[163][156][164]Socioeconomic status significantly influences bronchiectasis susceptibility, with higher rates observed in low-income settings where barriers to preventive healthcare exacerbate risks. In urban poor communities, inadequate vaccination coverage against childhood respiratory pathogens, such as Haemophilus influenzae type b and pneumococcus, contributes to recurrent infections that can lead to bronchiectasis; studies in low- and middle-income countries report prevalence up to three times higher among disadvantaged groups due to these gaps. Environmental pollution, including indoor biomass smoke and outdoor particulate matter, further amplifies vulnerability in these populations, as short-term exposures have been associated with increased mortality and disease progression in resource-limited urban areas.[165][166]Comorbidities like chronic obstructive pulmonary disease (COPD) substantially elevate bronchiectasis risk through shared etiological pathways. Overlap occurs in approximately 30% of COPD patients, driven by common exposures such as tobacco smoking and air pollution, which impair mucociliary clearance and promote chronic inflammation in the airways. This bronchiectasis-COPD overlap syndrome heightens susceptibility to exacerbations and severe airflow limitation, underscoring the need for targeted screening in at-risk individuals with obstructive lung disease.[167]Ethnic variations also play a role in bronchiectasis distribution, with elevated rates among indigenous populations such as Maori and Pacific Islanders. Hospital admission rates for bronchiectasis are 3.5 to 5 times higher in Maori compared to non-Maori New Zealanders, and similarly disproportionate among Pacific Islanders, who represent 20–26% of cases despite comprising smaller population shares. These disparities arise from intertwined genetic predispositions—such as variations in immune response genes—and environmental factors, including overcrowding, poor housing, and limited access to early interventions in these communities. These population-specific risks contribute to the heterogeneous global prevalence patterns of bronchiectasis.[168][152]
History
Early Descriptions
The earliest clinical recognition of what is now known as bronchiectasis dates to the 19th century, when Frenchphysician René-Théophile-Hyacinthe Laënnec provided the first detailed description based on autopsy findings and auscultation using his newly invented stethoscope.[44] In his 1819 treatise Traité de l'Auscultation Médiate, Laënnec coined the term "bronchiectasis," derived from the Greek words bronchi (airways) and ektasis (dilation), to describe the irreversible widening of the bronchi associated with chronic suppuration and foul-smelling sputum.[1] He observed these changes in patients with recurrent pulmonary infections, noting the pathological dilation as a consequence of prolonged inflammation, often linked to prior respiratory illnesses.Throughout the 19th century, bronchiectasis was increasingly documented as a complication of tuberculosis (TB) and other destructive lung conditions, with high mortality rates in the pre-antibiotic era. Physicians like William Osler further elaborated on its clinical features in the late 1800s, describing chronic cough, copious purulent sputum, and hemoptysis as hallmarks, often leading to respiratory failure or secondary infections.[44] A 1940 study of 400 patients reported a mortality rate higher than 30%, with most dying within 2 years of symptom onset and before age 40, primarily from overwhelming infections or cor pulmonale, underscoring the condition's severity before antimicrobial therapies emerged.[44]In the mid-20th century, pathologist Lynne Reid advanced the understanding through histological examinations, establishing definitive criteria for bronchiectasis in 1950 by classifying it into cylindrical, varicose, and saccular subtypes based on bronchial dilation severity and loss of muscular and elastic components. Reid's work, correlating gross pathology with bronchographic imaging, highlighted the role of recurrent infections in perpetuating airway destruction, particularly as a sequela of inadequately treated TB, which was a leading cause in that era. These descriptions laid the foundation for recognizing bronchiectasis as a distinct entity beyond mere post-infectious scarring.
Modern Understanding and Advances
The introduction of antibiotics in the 1940s marked a pivotal advancement in bronchiectasis management, dramatically reducing mortality rates from over 30% in untreated cases to significantly lower levels by controlling bacterial infections and preventing exacerbations.[169] Inhaled antibiotics, first explored during this era for chronic airway infections, laid the groundwork for targeted antimicrobial strategies that improved patient survival and quality of life.[170] By the 1950s, the association between cystic fibrosis (CF) and bronchiectasis was firmly established through pathological studies, such as those by Lynne Reid, which characterized the bronchial dilation and mucus plugging in CF as a primary driver of bronchiectasis progression.[171] This recognition shifted focus toward identifying underlying genetic causes, distinguishing CF-related bronchiectasis from other forms and enabling earlier interventions.Advancements in imaging further transformed diagnosis throughout the 20th century. Bronchography, introduced in the 1930s using iodized oil contrasts like Lipiodol, allowed direct visualization of bronchial abnormalities, confirming bronchiectasis in cases previously reliant on clinical symptoms alone.[172] However, its invasiveness limited widespread use until the 1980s, when high-resolution computed tomography (HRCT) emerged as a non-invasive gold standard, providing detailed cross-sectional images that revolutionized accurate detection and extent assessment of bronchiectasis with high sensitivity. Seminal studies in 1986 demonstrated HRCT's superiority over conventional radiography, enabling precise classification of cylindrical, varicose, and cystic subtypes and facilitating timely treatment.In the 21st century, real-world data initiatives like the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) registry, launched in 2012, have provided comprehensive insights into disease characteristics, exacerbations, and management across diverse populations, informing guidelines and highlighting gaps in non-CF bronchiectasis (NCFB) care.[173] For CF-related bronchiectasis, CFTR modulator therapies since 2012 have offered transformative benefits; the triple combination of elexacaftor, tezacaftor, and ivacaftor, approved in 2019, improved percent predicted forced expiratory volume in 1 second (ppFEV1) by approximately 14% in clinical trials and sustained lung function gains in real-world settings through 2025.[174]Recent efforts in 2024–2025 have addressed longstanding unmet needs in NCFB through targeted trials, culminating in the FDA approval of brensocatib, a dipeptidyl peptidase 1 inhibitor, as the first specific therapy to reduce pulmonary exacerbations by up to 20% and slow lungfunction decline in phase 3 studies.[24] This milestone, based on the ASPEN trial results, represents a shift toward disease-modifying agents that inhibit neutrophilic inflammation, filling critical gaps in therapeutic options beyond antibiotics and airway clearance.[175] Ongoing investigations into biologics, such as anti-IL-33 monoclonal antibodies, continue to explore anti-inflammatory pathways to further mitigate fibrosis and structural damage in NCFB.[176]