Bronchiectasis

Anatomical and Structural Changes

• The disease involves abnormal and permanent dilation of the proximal and medium-sized bronchi (typically those >2 mm in diameter), due to destruction of the elastic and muscular components of the bronchial wall.
• Histopathological findings include transmural inflammation, mucosal oedema, ulceration, scarring, and peribronchial fibrosis.
• Three morphological subtypes are described:
  • Cylindrical bronchiectasis: uniform, tubular bronchial dilation often described as “tram-track” on imaging.
  • Varicose bronchiectasis: irregular bronchial walls with alternating segments of dilation and constriction.
  • Cystic (saccular) bronchiectasis: the most severe form, with dilated bronchi terminating in ballooned sacs, sometimes with air-fluid levels or a “bunch-of-grapes” appearance on imaging.

Exacerbations and Disease Course

• Exacerbations are defined by acute worsening of symptoms such as increased sputum volume and purulence, breathlessness, and systemic symptoms like fatigue or malaise.
• These episodes are most commonly triggered by bacterial infections but may also follow viral respiratory tract infections.
• Repeated exacerbations accelerate lung function decline and contribute to the progression of structural damage.
• Patients chronically colonised with Pseudomonas aeruginosa or other resistant pathogens tend to have more severe exacerbations and poorer prognosis.

Post-Infectious Causes

• A history of severe or inadequately treated respiratory infections is a leading cause of bronchiectasis globally.
• Childhood infections such as measles, pertussis, respiratory syncytial virus, and adenovirus can lead to airway damage.
• Mycobacterial infections, particularly Mycobacterium tuberculosis and nontuberculous mycobacteria (e.g., Mycobacterium avium complex), are common triggers.
• Bacterial pathogens such as Staphylococcus aureus, Klebsiella species, and Haemophilus influenzae are known to cause necrotising pneumonias that may progress to bronchiectasis.
• Coronavirus disease (COVID-19) has been associated with post-viral airway damage in severe cases.

Airway Obstruction

• Focal bronchial obstruction may arise from inhaled foreign bodies, tumours, broncholithiasis, or extrinsic lymph node compression.
• Swyer-James syndrome (a post-infectious bronchiolitis obliterans) results in unilateral lung hypoplasia and hyperlucency.
• Right-middle lobe syndrome involves obstruction from lymphadenopathy or anatomical angulation, often following infection.

Aspiration

• Chronic or recurrent aspiration, often in patients with neurological impairment, reflux, or altered mental status, predisposes to focal airway inflammation and damage.
• Gastro-oesophageal reflux has been implicated, with some evidence linking Helicobacter pylori to aspiration-related lung injury.

Genetic Disorders

• Cystic fibrosis is a major cause of diffuse bronchiectasis in developed nations, driven by CFTR gene mutations causing defective chloride transport and mucociliary dysfunction.
• Primary ciliary dyskinesia includes Kartagener syndrome (situs inversus, chronic sinusitis, and bronchiectasis) and results from inherited ciliary structural or functional defects.
• Young syndrome mimics cystic fibrosis but lacks a CFTR mutation; it features obstructive azoospermia, sinusitis, and bronchiectasis.
• Alpha-1 antitrypsin deficiency is associated with bronchial wall destruction and airway colonisation, though less frequently than with emphysema.
• Autosomal dominant polycystic kidney disease may be associated with bronchiectasis as part of a ciliopathy.

Allergic and Immune-Mediated Conditions

• Allergic bronchopulmonary aspergillosis (ABPA) results from hypersensitivity to Aspergillus fumigatus and is associated with central bronchiectasis, eosinophilia, and raised IgE levels.
• Hypogammaglobulinaemia and specific immunoglobulin subclass deficiencies contribute to recurrent infections and progressive airway damage.
• Common variable immunodeficiency and other B-cell disorders are notable causes, especially when diagnosed in childhood.
• Human immunodeficiency virus (HIV) infection may predispose to bronchiectasis via recurrent infections and immune dysregulation.

Connective Tissue and Autoimmune Disorders

• Rheumatoid arthritis, systemic lupus erythematosus, and Sjögren syndrome are associated with bronchiectasis, often due to increased infection susceptibility or mucus hyperviscosity.
• Inflammatory bowel diseases such as ulcerative colitis and Crohn's disease have been linked to airway inflammation and bronchiectasis.
• Sarcoidosis, through parenchymal scarring or bronchial compression, and relapsing polychondritis may also contribute.
• Marfan and Ehlers-Danlos syndromes, through structural airway fragility, have been implicated in bronchiectatic changes.

Congenital and Structural Abnormalities

• Williams-Campbell syndrome involves congenital absence of cartilage in subsegmental bronchi, leading to airway collapse.
• Mounier-Kuhn syndrome (tracheobronchomegaly) results in dilated central airways with impaired clearance.
• Bronchopulmonary sequestration is a developmental anomaly leading to isolated lung segments prone to infection.

Environmental and Other Causes

• Inhalation of toxic gases, such as ammonia or chlorine, can result in direct airway injury and cystic bronchiectasis.
• Yellow nail syndrome, a rare condition involving lymphoedema and pleural effusions, is associated with bronchiectasis.
• Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides can damage the airways through small vessel inflammation.
• Human T-cell lymphotropic virus type 1 (HTLV-1) infection has been implicated in endemic bronchiectasis in some populations.

Idiopathic Bronchiectasis

• Despite thorough investigation, no cause is identified in up to 29% of adult patients.
• In children, causes are more often found, and idiopathic classification should be reserved for cases where all other evaluations have been exhausted.

Initial Insult and Host Immune Response

• The development of bronchiectasis typically begins with an infectious insult that interacts with impaired mucociliary clearance, airway obstruction, or host defence dysfunction.
• The airway epithelium responds by recruiting immune cells, predominantly neutrophils, which release elastase, myeloperoxidase, reactive oxygen species, and inflammatory cytokines such as IL-8 and IL-1β.
• These mediators promote transmural inflammation, mucosal oedema, ulceration, and eventual structural deterioration of the bronchial wall, including damage to elastic and muscular layers.
• Chronic inflammation also triggers neovascularisation and cratering within the airways, contributing to haemoptysis in some patients.

The Vicious Cycle and the Vicious Vortex

• The concept of the “vicious cycle” describes how infection and inflammation reinforce one another, leading to bronchial wall destruction and abnormal dilation.
• This model has evolved into the “vicious vortex”, reflecting the multidirectional interactions among four interconnected processes:
  • Epithelial and ciliary dysfunction with mucus hypersecretion
  • Chronic bacterial colonisation and biofilm formation
  • Persistent neutrophilic inflammation with cytokine and protease release
  • Impaired mucociliary clearance sustaining infection and injury

Structural and Cellular Changes

• Histopathological features include transmural inflammation with neutrophil predominance, peribronchial fibrosis, and airway wall thickening.
• Mononuclear infiltration comprising CD4+ T cells and CD68+ macrophages is also commonly observed.
• Over time, mucous glands hypertrophy and goblet cell hyperplasia occur, leading to further mucus accumulation and airway obstruction.
• Bronchiectatic airways become highly susceptible to colonisation, particularly by Pseudomonas aeruginosa, which is associated with accelerated disease progression and increased mortality.

Neutrophil Dysfunction and NETs

• Neutrophils in bronchiectatic airways show prolonged viability and impaired phagocytosis, especially in the presence of Pseudomonas.
• Neutrophil extracellular traps (NETs), composed of DNA, histones, elastase, and pregnancy zone protein (PZP), form part of the innate immune response but also exacerbate tissue injury.
• Elevated NET levels are associated with symptom severity and can persist despite antibiotic therapy, particularly when Pseudomonas is the colonising organism.

Airway Secretions and Mucus Properties

• Bronchiectasis is associated with tenacious, highly viscous sputum that contains high levels of mucin (predominantly MUC5B), DNA, and inflammatory proteins.
• The presence of IL-1β in sputum correlates with disease severity and contributes to mucus hyperconcentration.
• Variability in sputum rheology helps explain differences in response to airway clearance strategies across patients.
• Studies in high-prevalence populations, such as Alaska Native children, have demonstrated differences in sputum transportability that may contribute to divergent disease trajectories.

Influence of Atopy and Immunogenetics

• Atopy has been implicated in worsening disease severity. Patients with multiple allergen sensitivities (excluding those with ABPA) have lower lung function and worse scores on severity indices.
• Heterozygous variants of the CFTR gene, even in the absence of cystic fibrosis, may predispose to abnormal ion transport in the airway epithelium, contributing to mucus retention and infection.
• Nasal potential difference studies show intermediate phenotypes in patients with one CFTR mutation, suggesting subclinical CFTR dysfunction may be relevant in a subset of bronchiectasis cases.

Systemic Modifiers of Inflammation

• Vitamin D deficiency has been associated with increased frequency of exacerbations, more severe symptoms, and enhanced neutrophilic inflammation.
• In one study, over 90% of bronchiectasis patients were either vitamin D deficient or insufficient. The vitamin D–deficient group had higher rates of Pseudomonas colonisation and worse clinical scores.
  The immunomodulatory role of vitamin D remains under investigation, with hypotheses suggesting a link to impaired innate immunity and reduced mucosal defences.

Early Pathological Changes in Immunodeficient States

• In patients with common variable immunodeficiency (CVID), small airway abnormalities such as mosaic attenuation and air trapping can be detected on high-resolution CT scans before overt bronchiectasis develops.
• These changes suggest a pre-bronchiectatic phase of disease, highlighting the importance of early detection and immune modulation in susceptible populations.

Global and Regional Prevalence

• Worldwide prevalence is difficult to determine due to limited data from low-resource settings where underdiagnosis is common, and access to imaging and specialist care is restricted.
• In the United Kingdom, approximately 212,000 individuals are currently affected, with rising detection rates linked to greater awareness and increased imaging use.
• United States estimates vary widely, ranging from 100,000 based on older data to more recent figures suggesting 340,000 to 522,000 adults receiving treatment, with up to 67% of cases occurring in women and 76% in individuals aged 65 years or older.
• In Germany and other high-income countries, age-specific data mirror these trends, with prevalence rising significantly in older age groups.

Age-Related Trends

• Prevalence increases with age, from approximately 7 per 100,000 in young adults aged 18–34 years to over 800 per 100,000 in individuals older than 75.
• A Medicare study in the US reported an annual prevalence of 701 per 100,000 persons aged 65 years and older.
• Similar age gradients have been observed in Denmark, Germany, and the UK, highlighting bronchiectasis as a predominantly disease of ageing.

Sex and Ethnic Patterns

• Non–cystic fibrosis bronchiectasis is more frequently observed in women, particularly slender white women aged over 60, where Mycobacterium avium complex infection has been identified as a common aetiology.
• Indigenous populations such as Native Americans in Alaska show higher-than-expected prevalence, up to four times that of the general population, likely due to increased exposure to childhood infections, limited healthcare access, and environmental factors.
• A New Zealand study found an incidence of 3.7 per 100,000 children, with significantly higher rates among Pacific children (17.8 per 100,000), emphasising ethnic disparities.

Childhood-Onset Disease

• Over 60% of adults with bronchiectasis report symptom onset in childhood. These individuals tend to have more severe disease and worse outcomes than those with adult-onset bronchiectasis.
• In many cases, early manifestations are linked to infections, immune deficiencies, or congenital abnormalities, often going undiagnosed until adulthood.

Impact on Healthcare Systems

• Bronchiectasis is associated with high rates of healthcare utilisation, including outpatient visits, imaging, antibiotic prescriptions, and hospital admissions.
• Hospitalisation, especially in those with frequent exacerbations or chronic Pseudomonas aeruginosa colonisation, contributes significantly to economic burden.
• Individuals with bronchiectasis and coexisting chronic obstructive pulmonary disease experience more hospitalisations and worse health outcomes than those with either disease alone.

Changing Epidemiological Patterns

• The rise in diagnosed bronchiectasis in high-income countries has been partially attributed to enhanced recognition and more widespread use of high-resolution computed tomography.
• There is also growing recognition of bronchiectasis associated with atypical infections, including nontuberculous mycobacteria and Pseudomonas, which may have contributed to the increased incidence in recent decades.
• An epidemiological review of hospitalisation rates in the US found a rising trend from 1993 to 2006, particularly among patients over 60 years of age.

Underserved and High-Burden Regions

• In resource-limited settings such as Oceania, rural India, and the Arctic, bronchiectasis remains a major cause of chronic lung disease and early mortality.
• Environmental exposures, smoke inhalation, and delayed access to antibiotics for respiratory infections likely exacerbate disease progression.
• Public health disparities and limited access to early diagnosis continue to drive worse outcomes in these populations.

Chronic Cough

• Cough is the most prevalent symptom, occurring in approximately 98% of adult patients. It is typically persistent, present for months or years, and may worsen when lying flat or during exacerbations.
• Children may present with a chronic wet cough, and failure to respond to antibiotics should prompt investigation for underlying bronchiectasis.

Sputum Production

• Daily expectoration of mucoid or purulent sputum is present in two-thirds of patients, with production increasing during acute respiratory infections.
• Sputum is often relatively odourless during stable disease, but becomes purulent and occasionally foul-smelling during exacerbations.
• Haemoptysis, usually mild (blood-streaked sputum), occurs in up to 92% of patients and may be the initial reason for seeking medical attention.

Dyspnoea

• Breathlessness is reported by 60% to 72% of patients and is typically exertional. It correlates with radiographic disease severity and may also reflect concurrent COPD or asthma.
• Severe dyspnoea is uncommon in children but, if present, suggests a significant exacerbation.

Recurrent Infections and Exacerbations

• Many patients describe frequent respiratory infections that respond temporarily to antibiotics.
• Exacerbations are often heralded by increased sputum production, purulence, dyspnoea, fatigue, fever, and occasionally pleuritic pain.

Fatigue and Malaise

• Fatigue is common and may relate to systemic inflammation, nocturnal coughing, or poor sleep quality.

Pleuritic Chest Pain

• Experienced by approximately 20% of patients, typically during periods of excessive coughing or acute infection.

Wheezing

• Present in about 25% of adults and may reflect airflow obstruction or coexisting asthma.

Weight Loss and Constitutional Symptoms

• Weight loss is a non-specific finding that suggests severe or advanced disease.
• Other constitutional symptoms include weakness, low-grade fever, and, in women, urinary incontinence related to chronic coughing.

Historical Risk Factors Suggestive of Underlying Aetiology

Cystic Fibrosis

• The most common identifiable cause, especially in children and young adults. Adults may present with bronchiectasis as the first manifestation, particularly those with atypical or milder genotypes.
• Associated features include sinusitis, pancreatic insufficiency, and colonisation with Pseudomonas aeruginosa or Staphylococcus aureus.

Primary Ciliary Dyskinesia and Kartagener Syndrome

• Patients often report recurrent ear, sinus, and chest infections from early childhood.
• Kartagener syndrome features situs inversus, sinusitis, and bronchiectasis.

Congenital Airway Disorders

• Conditions such as Young syndrome, Williams-Campbell syndrome, and Mounier-Kuhn syndrome may present with chronic respiratory symptoms early in life or in young adulthood.

Immunodeficiency

• Congenital (e.g. IgG subclass deficiency, IgA or IgM deficiency) or acquired (e.g. HIV) immunodeficiencies predispose to recurrent infections and diffuse bronchiectasis.

Previous Infections

• A history of severe childhood infections—tuberculosis, pertussis, measles, or pneumonia—should raise suspicion.
• Swyer-James or Macleod syndrome may arise from post-adenoviral bronchiolitis in childhood.

Allergic Bronchopulmonary Aspergillosis (ABPA)

• Considered in patients with asthma and frequent pulmonary infections.
• Often presents with productive cough and intermittent haemoptysis.

Connective Tissue Diseases

• Rheumatoid arthritis, Sjögren syndrome, Ehlers-Danlos, and Marfan syndrome may be linked to bronchiectasis.
• In RA, lung disease may precede systemic features.

Inflammatory Bowel Disease

• Ulcerative colitis has a stronger association than Crohn’s disease.
• Patients may report chronic cough or infections.

Aspiration or Inhalation Injury

• Repeated aspiration events, particularly in patients with reflux, neurological disorders, or poor dentition, can lead to focal bronchiectasis.

Focal Obstruction

• History suggesting endobronchial tumour, foreign body, or lymphadenopathy causing airway compression should prompt focused investigation.

Non-Tuberculous Mycobacterial Infection

• Tall, thin, older white women are at increased risk, sometimes referred to as having "Lady Windermere syndrome".
• Associated features include scoliosis and mitral valve prolapse.

Prematurity

• Children born preterm are at higher risk of developing bronchiectasis due to impaired lung development.

Auscultation

• Crackles are the most common physical sign, present in approximately 73% to 75% of patients. They are often bi-basal and may be more pronounced during active infection or exacerbation.
• High-pitched inspiratory squeaks and pops are also commonly heard and may suggest airflow through narrowed or mucus-plugged airways.
• Rhonchi may be heard during periods of increased mucus secretion or airway obstruction.
• Wheezing occurs in about 22% to 33% of patients. It may result from mucus-related obstruction, structural airway collapse, or coexisting asthma or COPD.
• Localised wheeze may suggest an obstructing lesion such as a tumour or foreign body.

Digital Clubbing

• Clubbing is uncommon and found in only 2% to 3% of cases.
• When present, it is more frequent in patients with moderate-to-severe disease and typically correlates with chronic hypoxia or coexistent conditions.

Signs of Advanced Disease

• Cyanosis and plethora may be observed in rare cases, secondary to polycythaemia from chronic hypoxaemia.
• Wasting and unintentional weight loss may indicate a high disease burden, often associated with frequent exacerbations or increased caloric demands due to the effort of coughing.
• Right-sided heart failure (cor pulmonale) may be evident in severe disease, including signs such as peripheral oedema, hepatomegaly, and hypoxaemia.

Upper Airway Findings

• Nasal polyps and features of chronic rhinosinusitis are commonly seen in patients with cystic fibrosis, primary ciliary dyskinesia, and other mucociliary clearance disorders.
• Examination of the nasal passages and sinuses may reveal mucosal swelling, discharge, or structural abnormalities.

Reproductive and Systemic Features

• In men, infertility may be a feature of associated conditions like primary ciliary dyskinesia or Young syndrome.
• Women may report urinary incontinence, particularly during coughing episodes. This has been reported in nearly half of female bronchiectasis patients in some studies.
• A reduced sense of smell is often reported in patients with chronic rhinosinusitis or primary humoral immunodeficiency.

Musculoskeletal and Rheumatological Findings

• In patients with rheumatoid arthritis, joint examination may reveal arthritis or the Sicca complex (dry eyes and dry mouth).
• Patients with Ehlers-Danlos or Marfan syndrome may exhibit hypermobility, tall stature, or characteristic body habitus.

Findings Suggestive of Associated Aetiologies

• ABPA may present with prominent wheezing and signs consistent with asthma.
• Localised findings such as unilateral wheeze or diminished breath sounds may indicate bronchial obstruction.
• Chronic sinus disease and recurrent otitis media in conjunction with bronchiectasis suggest primary ciliary dyskinesia or cystic fibrosis.

Features of Acute Exacerbation

• Increased volume or purulence of sputum.
• Change in sputum colour, often to green or yellow, indicating neutrophilic inflammation.
• New or worsening dyspnoea.
• Fever and malaise.
• Increased wheezing and decline in pulmonary function (often confirmed with spirometry or peak flow).

Imaging

High-Resolution Chest CT (HRCT)

• HRCT is the gold standard for diagnosing bronchiectasis.
• Reveals hallmark features including airway dilation, bronchial wall thickening, lack of tapering, and peripheral visibility of bronchi.
• The signet ring sign (bronchus diameter > adjacent pulmonary artery) is a key radiologic marker.
• Other characteristic findings include tram-track appearance, tree-in-bud pattern, cystic changes, and varicose dilations.
• Multidetector CT (MDCT) is preferred in children due to its ability to produce thin sections with less radiation exposure.
• Contrast-enhanced CT may show dilated bronchial arteries, often the source of haemoptysis.

Chest Radiograph (CXR)

• Often non-specific but may show volume loss, tram lines, ring shadows, or tubular/ovoid opacities.
• Useful as a baseline or in acute deterioration.
• In children, CXR can help exclude pneumonia or foreign body aspiration.

Microbiological Testing

Sputum Culture and Sensitivity

• Essential for identifying bacterial, fungal, and mycobacterial pathogens.
• Pseudomonas aeruginosa is the most frequently isolated organism and associated with worse prognosis, especially the mucoid phenotype.
• Other common isolates include Haemophilus influenzae, Staphylococcus aureus, Klebsiella pneumoniae, Moraxella catarrhalis, and Mycobacterium avium complex.
• Special culture media may be required for non-tuberculous mycobacteria and fungal organisms.

Bronchoscopy with Bronchoalveolar Lavage (BAL)

• Used when sputum samples are inconclusive or a foreign body is suspected.
• May aid in diagnosing NTM infection or malignancy.

Blood Tests

Complete Blood Count (CBC)

• Neutrophilia may suggest acute infection; eosinophilia raises suspicion for allergic bronchopulmonary aspergillosis (ABPA).
• Anaemia is common in chronic disease; polycythaemia may occur in advanced hypoxic cases.

Serum Immunoglobulins

• Total IgG, IgA, IgM and IgG subclasses should be measured to assess for hypogammaglobulinaemia.
• Poor vaccine response, especially to Streptococcus pneumoniae, supports antibody deficiency.
• Immunoglobulin replacement therapy is beneficial in selected patients.

Alpha-1 Antitrypsin (AAT) Levels and Phenotype

• Indicated in patients with basal panacinar emphysema or early-onset COPD.
• Deficiency increases susceptibility to bronchial damage.

Sweat Chloride Test and CFTR Mutation Analysis

• Recommended in all children and adults with suggestive features, particularly younger patients with upper lobe disease or Pseudomonas colonisation.
• Sweat chloride ≥60 mmol/L is diagnostic for cystic fibrosis.
• Intermediate results warrant CFTR gene testing.

Tests for Allergic Bronchopulmonary Aspergillosis (ABPA)

• Total serum IgE, specific IgE and IgG to Aspergillus fumigatus, and skin prick testing.
• IgE >1000 IU/mL or doubling from baseline supports diagnosis.

HIV Antibody Test

• Important for identifying acquired immunodeficiency as a risk factor for recurrent infections and bronchiectasis.

Autoimmune Serology

• ANA, rheumatoid factor, and other autoantibodies may be indicated if connective tissue disease is suspected.
• Not routinely recommended unless clinically indicated.

Nasal Nitric Oxide (NNO) Testing

• Low levels suggest primary ciliary dyskinesia (PCD) if cystic fibrosis is excluded.
• NNO has high sensitivity and specificity and is preferred in cooperative children ≥5 years.

Pulmonary Function Testing

Spirometry and Lung Volumes

• Obstructive pattern is most common (reduced FEV1 and FEV1/FVC).
• FEV1 decline is associated with disease severity, especially in Pseudomonas colonisation.
• Air trapping (increased residual volume) and reduced diffusing capacity (DLCO) may be present in advanced disease.
• Bronchodilator reversibility testing can identify coexistent asthma.

6-Minute Walk Test

• Assesses functional capacity and exercise-induced desaturation.

Aetiological and Supportive Investigations

Electron Microscopy and Ciliary Function Tests

• Sperm and respiratory epithelium examined for ultrastructural defects in suspected PCD.

CFTR Genetic Testing

• Used following intermediate sweat chloride levels or atypical CF presentation.

Swallow Study and Oesophageal pH Monitoring

• Evaluate for chronic aspiration, especially in children or those with neurological impairment.

Bone Mineral Density

• Low bone density is common, especially in younger patients and those with frequent exacerbations.

Diagnostic Criteria for Bronchiectasis

Clinical Criteria

• At least two of the following:
  • Cough on most days
  • Sputum production on most days
  • Recurrent exacerbations

Radiological Criteria (on HRCT)

• Airway-to-artery ratio ≥1.0–1.5
• Lack of bronchial tapering
• Visibility of peripheral bronchi within 1 cm of the pleura
• Cylindrical, varicose, or cystic bronchial dilation

Distribution Clues to Aetiology

• Lower lobe: Post-infectious causes
• Upper lobe: Cystic fibrosis, tuberculosis, fungal infections
• Central: ABPA
• Right middle lobe: Right middle lobe syndrome or mechanical obstruction

Chronic Obstructive Pulmonary Disease (COPD)

• Breath sounds are typically diminished in COPD, in contrast to the crackles and inspiratory squeaks often present in bronchiectasis.
• Rhonchi may be heard in both conditions, but inspiratory squeaks are more specific to bronchiectasis.
• HRCT in COPD may show emphysema or hyperinflation, whereas bronchiectasis shows thickened and dilated airways, varicose constrictions, cystic changes, or tree-in-bud patterns.
• Coexistence of COPD and bronchiectasis is recognised and associated with worse clinical outcomes.

Asthma

• Asthma is characterised by episodic wheezing, reversible airflow obstruction, and a response to bronchodilators.
• Inspiratory squeaks and crackles, common in bronchiectasis, are not typical features of asthma.
• HRCT may show airway wall thickening in asthma but lacks hallmark features such as the signet ring sign or cystic dilation seen in bronchiectasis.
• Patients with severe or poorly controlled asthma may develop secondary bronchiectasis.

Pneumonia

• Pneumonia usually presents acutely, with symptoms developing over 7 to 10 days, compared to the chronic symptomatology of bronchiectasis.
• Bronchial breath sounds and consolidation, key findings in pneumonia, are not features of bronchiectasis.
• HRCT in pneumonia shows focal consolidation, air bronchograms, or infiltrates, while bronchiectasis is defined by airway dilation and lack of tapering.
• Both conditions may coexist during exacerbations, but the underlying pathophysiology and treatment differ.

Chronic Sinusitis

• While sinus involvement is common in bronchiectasis related to mucociliary defects, chronic sinusitis alone does not typically cause pulmonary symptoms.
• Inspiratory squeaks and crackles are rare in isolated chronic sinusitis.
• Sinus CT may reveal sinus opacification, but chest imaging remains normal unless there is coexisting lower respiratory tract involvement.

Cystic Fibrosis

• A major cause of bronchiectasis, particularly in children and young adults.
• Diagnosis relies on sweat chloride testing and/or CFTR gene mutation analysis.
• CF-related bronchiectasis typically affects the upper lobes and may present with recurrent infections, pancreatic insufficiency, and sinus disease.

Alpha-1 Antitrypsin Deficiency

• May present with basal emphysema and early-onset COPD, occasionally complicated by bronchiectasis.
• Confirmed by measuring serum AAT levels and phenotyping.
• Suggestive features include early age of onset and absence of smoking history.

Aspiration Pneumonitis and Pneumonia

• History of dysphagia, gastro-oesophageal reflux, or neurologic impairment supports this diagnosis.
• HRCT may show focal infiltrates in dependent lung zones.
• Chronic aspiration can result in focal bronchiectasis, requiring swallow studies and pH monitoring for confirmation.

Tuberculosis (TB)

• TB can cause post-infectious upper lobe bronchiectasis.
• Sputum cultures and chest imaging are essential for diagnosis.
• Cavitation, calcified lymph nodes, and apical fibrosis are more typical of TB than bronchiectasis.

Bronchitis

• Acute bronchitis is typically self-limiting and presents with transient symptoms.
• Chronic bronchitis, a form of COPD, presents with a productive cough for at least three months per year for two consecutive years.
• HRCT is usually normal or shows only mild changes, lacking the airway dilation seen in bronchiectasis.

Gastroesophageal Reflux Disease (GERD)

• Chronic microaspiration due to GERD may contribute to the development of bronchiectasis.
• Evaluation with pH monitoring and swallow studies may reveal silent aspiration.
• GERD alone does not cause airway dilation or bronchial wall thickening.

Emphysema

• A subtype of COPD primarily characterised by alveolar destruction and hyperinflation.
• HRCT reveals low-attenuation areas without airway wall thickening or dilatation.
• Breath sounds are often reduced, and wheeze may be present; crackles are less typical.

Parapneumonic Effusions and Empyema

• These are complications of pneumonia rather than primary lung diseases.
• Imaging reveals pleural fluid collections rather than airway changes.
• Thoracentesis and pleural fluid analysis aid in diagnosis.

Overview and Goals of Therapy

• Management consists of long-term maintenance strategies, treatment of acute exacerbations, and targeted interventions based on underlying cause or identified pathogens.
• Primary goals are to reduce symptoms (cough, sputum, dyspnoea), improve quality of life, prevent exacerbations, and limit disease progression.
• Children and adolescents require early intervention, tailored airway clearance approaches, and caregiver involvement to optimise outcomes.
• Treatment must also address comorbid conditions such as cystic fibrosis, gastro-oesophageal reflux, or immunodeficiency.

Maintenance 

Airway Clearance Techniques (ACTs)

• Essential for improving mucus drainage and reducing exacerbation frequency.
• Techniques include active cycle breathing, autogenic drainage, postural drainage, percussion, oscillatory PEP devices (e.g. flutter valve, Acapella), and high-frequency chest wall oscillation.
• Gravity-assisted positioning enhances efficacy.
• Recommended duration: 15–30 minutes, 2–3 times daily.
• Children require age-appropriate techniques and regular review by a paediatric respiratory physiotherapist.
• Use of a short-acting bronchodilator prior to ACT may help in asthma-like features or airway hyperreactivity.

Exercise and Diet

• Regular physical activity is recommended for all patients and may function as adjunctive airway clearance.
• Pulmonary rehabilitation improves exercise capacity and short-term quality of life.
• Vitamin D supplementation is advised.
• In children, exercise should be promoted as part of normal play without rigid regimens.

Self-Management Plans

• Encourage patients to recognise exacerbations and initiate early treatment.
• Action plans include details on symptom monitoring, sputum collection, and emergency use of rescue antibiotics.
• Evidence is extrapolated from COPD and asthma; formal studies in bronchiectasis are ongoing.

Targeted Maintenance Therapy

Eradication of Pseudomonas aeruginosa

• Early aggressive treatment upon first or new isolation is recommended.
• Eradication regimens vary but often include:
  • Oral ciprofloxacin (14 days), followed by inhaled antibiotics (e.g., colistimethate, tobramycin)
  • IV antibiotics (e.g., ceftazidime + tobramycin) followed by nebulised antibiotics for 3 months
• Repeat sputum cultures guide next steps.
• ERS and BTS recommend eradication therapy even if the patient is clinically stable, after shared decision-making.

Long-Term Antibiotics

• Indicated in patients with ≥3 exacerbations per year.
• Macrolides (e.g. azithromycin, erythromycin):
  • Reduce exacerbations and sputum volume.
  • Require ECG and liver function tests prior to initiation and monitoring for QTc prolongation and hepatotoxicity.
  • Pause annually (e.g. summer break) may reduce resistance risk.
• Inhaled antibiotics (e.g. tobramycin, gentamicin, colistimethate):
  • Reduce bacterial load and may be combined with macrolides.
  • Must be guided by culture and sensitivity.
• Doxycycline or amoxicillin/clavulanate may be considered if macrolides are not tolerated.
• Fluoroquinolones are effective but carry serious adverse risks (e.g. tendon rupture, neuropathy) and should be reserved for resistant infections.

Mucoactive Agents

• Hypertonic saline: Improves mucus clearance but may cause bronchospasm. Addition of hyaluronic acid may improve tolerability.
• Mannitol: Limited benefit in trials; may be used in selected adults after tolerance assessment.
• Other mucolytics (e.g. acetylcysteine, erdosteine): May offer benefit in selected adults.
• rhDNase: Contraindicated in bronchiectasis as it increases exacerbations.
• In children, routine use is not recommended, except in severe disease under supervision.

Inhaled Corticosteroids (ICS)

• Not routinely indicated unless there is coexistent asthma, COPD, or ABPA.
• May reduce sputum production and inflammation but increase risk of infection, particularly non-tuberculous mycobacteria.

Bronchodilators

• Useful prior to ACT or inhaled therapies in patients with reversible airway obstruction.
• Should follow standard COPD or asthma guidelines in comorbid cases.

Treatment of Acute Exacerbations

Clinical Features

• Defined by worsening cough, increased sputum volume or purulence, fever, and malaise.
• In children: ≥3 days of increased symptoms, or any duration of dyspnoea/hypoxia in immunocompromised children.

Antibiotic Therapy

• Empirical treatment should be guided by prior sputum cultures.
• First-line oral agents:
  • S. pneumoniae: amoxicillin
  • H. influenzae: amoxicillin/clavulanate
  • Moraxella catarrhalis: amoxicillin/clavulanate or macrolides
  • P. aeruginosa: ciprofloxacin (oral) or ceftazidime/piperacillin-tazobactam (IV)
• MRSA: doxycycline, rifampicin, or trimethoprim/sulfamethoxazole; linezolid as second-line
• Duration: usually 14 days
• Intravenous therapy is indicated in severe cases, treatment failure, or infections with resistant organisms.

Adjunctive Measures

• Intensified airway clearance during exacerbations.
• Bronchodilators may be added for symptom relief.
• Systemic corticosteroids are not recommended unless indicated for another condition (e.g. ABPA).

Refractory Disease and Surgical Options

Surgical Resection

• Considered in localised disease unresponsive to maximal medical therapy or recurrent haemoptysis.
• Most effective when disease is focal and not driven by systemic disorders.
• Rarely indicated in children and only after multidisciplinary review.

Respiratory Failure Management

• Long-term oxygen therapy in line with COPD criteria.
• Domiciliary non-invasive ventilation for hypercapnic respiratory failure with recurrent admissions.

Lung Transplantation

• Consider in patients under 65 years with FEV₁ <30%, rapidly progressive disease, or complications such as massive haemoptysis, pulmonary hypertension, or respiratory failure.
• Referral should not be delayed in high-risk patients.

Severity Assessment

Bronchiectasis Severity Index (BSI)

• Incorporates age, BMI, FEV₁, prior hospitalisations, exacerbation frequency, breathlessness, colonisation with P. aeruginosa, and radiological severity.
• Preferred over FACED score as it includes exacerbation burden and predicts morbidity and mortality.

Disease Course and Long-Term Outlook

• Bronchiectasis is a chronic, irreversible condition in adults.
• In children and adolescents, early diagnosis and prompt treatment may lead to partial or full reversibility, especially in non-cystic fibrosis cases.
• The disease typically follows a relapsing course with intervals of clinical stability interrupted by exacerbations.
• Prognosis varies significantly depending on aetiology, comorbidities, and treatment adherence.

Factors Associated with Poor Prognosis

• Advanced age and male sex are consistently associated with higher mortality.
• Colonisation with Pseudomonas aeruginosa has been linked to more severe disease, lower FEV₁, increased frequency of exacerbations, and higher mortality.
• Frequent severe exacerbations are associated with accelerated lung function decline.
• Hypoxaemia, hypercapnia, and extensive radiological involvement independently predict increased mortality.
• Comorbid COPD or underlying rheumatological disease, especially rheumatoid arthritis, significantly increases the risk of death.
• Poor physical activity levels and higher residual volume/total lung capacity (RV/TLC) ratios correlate with worse outcomes.
• Increased bacterial diversity in sputum samples has also been associated with higher mortality.

Protective Factors

• Higher baseline body mass index is associated with improved survival.
• Routine vaccinations and regular physician visits contribute to reduced mortality.
• Early initiation of airway clearance, antibiotic treatment, and monitoring improve prognosis.

Prognostic Scoring Systems

• Bronchiectasis Severity Index (BSI): Predicts morbidity, mortality, and hospitalisation.
  • Incorporates age, BMI, FEV₁ %, number of exacerbations, colonisation with P. aeruginosa or other pathogens, hospitalisations, dyspnoea score (MRC), and radiological severity.
• FACED score: Also used to stratify disease severity, though it does not account for exacerbation frequency and is therefore less preferred for guiding treatment.

Quality of Life Considerations

• Symptoms such as daily sputum production, dyspnoea, and reduced FEV₁ have the greatest impact on health-related quality of life, as measured by the St. George’s Respiratory Questionnaire.
• Exacerbations are a major determinant of diminished quality of life in both adults and children, according to patient surveys.

Mortality Data

• In the pre-antibiotic era, bronchiectasis was associated with a high mortality rate, often exceeding 30% within two years of diagnosis.
• Contemporary mortality rates vary. A 1981 study reported 13% mortality after diagnosis, and a Finnish study in the 1990s found no increased mortality compared to asthma.
• A five-year follow-up of 245 patients with non-CF bronchiectasis reported an overall mortality rate of 20.4%.
  • This rose to 55% in patients with coexistent COPD.
  • Rheumatological disease conferred a sevenfold increased risk of death compared to patients without such comorbidities.
• Common causes of death include progressive respiratory failure, cor pulmonale, and complications such as recurrent pneumonia or massive haemoptysis.

Lung Transplantation

• Lung transplantation is an option for selected patients with advanced, refractory disease.
• Candidates include those younger than 65 years with FEV₁ <30% and/or severe clinical deterioration despite maximal therapy.
• A retrospective review reported 1-, 5-, and 10-year post-transplant survival rates of 87%, 53%, and 16%, respectively, with median survival of 6 years, comparable to other transplant indications.

Respiratory Failure

• As the disease advances, repeated infections and airway damage can compromise pulmonary function, leading to acute or chronic respiratory insufficiency.
• Management focuses on correcting hypoxaemia, supporting ventilation, and addressing the underlying trigger, typically infection or mucus obstruction.
• Oxygen therapy, bronchodilators, and, in more severe cases, non-invasive or mechanical ventilation may be required.
• Although rare in paediatric cases, respiratory failure may occur in children with extensive disease or delayed diagnosis.

Cor Pulmonale

• Sustained low oxygen levels may lead to pulmonary vascular remodelling and increased pulmonary artery pressures, culminating in right heart dysfunction (cor pulmonale).
• Features include peripheral oedema, hepatomegaly, and exertional dyspnoea.
• Long-term oxygen supplementation and diuretic therapy form the cornerstone of treatment.
• In cases unresponsive to medical management, transplant referral may be necessary.
• Paediatric cases are rarely affected if early therapeutic strategies are implemented.

Massive Haemoptysis

• Life-threatening bleeding from the airways, usually exceeding 250 mL in 24 hours, may occur due to erosion or rupture of dilated bronchial arteries.
• Emergency treatment includes placing the bleeding lung in the dependent position, securing the airway, and providing haemodynamic support.
• Definitive intervention may involve bronchial artery embolisation or surgical resection.
• Though haemoptysis is common in bronchiectasis, massive haemoptysis is rare and requires urgent specialist input.
• Children are very rarely affected by this complication.

Ischaemic Stroke

• Emerging evidence suggests that individuals with bronchiectasis are at increased risk of developing ischaemic stroke, possibly due to systemic inflammation or vascular dysfunction.
• One large cohort study reported a significantly elevated hazard ratio for stroke among patients with bronchiectasis compared to those without.
• Stroke risk should be assessed and managed as part of the broader care plan, particularly in older patients or those with cardiovascular risk factors.
• This complication is extremely rare in paediatric populations.

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