Prevalence

• Bronchiectasis is Found in Patients of All Ages, Genders, and Ethnic Groups
  • However, Older Adults are More Commonly Affected than Younger Age Groups

Sex

• Females are More Commonly Affected than Males in North America

Relative Prevalence of Specific Etiologies

• Post-infectious cases are uncommon in USA (except in Native Americans in Alaska) but are common in underdeveloped countries
• Over 50% of Bronchiectasis cases are idiopathic
• Approximately 25-30% of Bronchiectasis cases can be traced to a prior pulmonary infection

Association with Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)

• Patients with Moderate-Severe COPD Have an Increased Risk of Bronchiectasis (Chest, 2011) [MEDLINE]
• These Patients Have Severe Airflow Obstruction, Isolation of a Pathogenic Organism from Sputum, and at Least One Hospital Admission for an Exacerbation in the Prior Year
• These Patients Also Have an Increased Mortality Rate (Hazard Ratio: 2.54) (Am J Respir Crit Care Med, 2013) [MEDLINE]

Idiopathic

• Over 50% of All Bronchiectasis Cases are Idiopathic

Immunodeficiency

Hypogammaglobulinemia (see Hypogammaglobulinemia)

• Agammaglobulinemia (see Agammaglobulinemia)
  • Autosomal Recessive Agammaglobulinemia: severe hypogammaglobulinemia, antibody deficiency, and increased susceptibility to infection
  • X-Linked Agammaglobulinemia (Bruton Agammaglobulinemia): severe hypogammaglobulinemia, antibody deficiency, and increased susceptibility to infection
    • Most cases do not present prior to 6 mo of age
• Ataxia-Telangiectasia (see xxx)
• B-Cell Lymphoma (see Lymphoma): due to increased catabolism of immunoglobulins
• Biallelic Deficiency of Mismatch Repair Protein PMS2
• Common Variable Immunodeficiency (CVID) (see Common Variable Immunodeficiency): most cases do not present until the third or fourth decade of life
• Drug-Related Hypogammaglobulinemia: these cases probably occur in specific predisposed individuals
  • Captopril (see Captopril): may cause IgA deficiency
  • Carbamazepine (Tegretol) (see Carbamazepine): may cause IgA deficiency or reversible hypogammaglobulinemia
  • Chlorpromazine (Thorazine) (see Chlorpromazine): may cause IgA deficiency
  • Hydroxychloroquine (Plaquenil) (see Hydroxychloroquine): may cause IgA deficiency
  • Lamotrigine (Lamictal) (see Lamotrigine): may cause reversible hypogammaglobulinemia
  • Penicillamine (see Penicillamine): may cause IgA deficiency
  • Phenytoin (Dilantin) (see Phenytoin): may cause IgA deficiency or reversible hypogammaglobulinemia
  • Ramipril (Altace) (see Ramipril): may cause hypogammaglobulinemia
  • Sulfasalazine (see Sulfasalazine): may cause IgA deficiency
  • Valproic Acid (Depakote, Depakene) (see Valproic Acid): may cause IgA deficiency
• Good Syndrome (Immunodeficiency with Thymoma) (see Thymoma)
  • Physiology: B-cell immunodeficiency syndrome
  • Clinical
    • Hypogammaglobulinemia (see Hypogammaglobulinemia)
    • Thymoma (see Thymoma): usually spindle cell histology
• Hyper-IgM Syndrome
  • CD40 Ligand (CD40L or CD154) Deficiency: this X-linked disorder is the etiology of most cases of Hyper-IgM syndrome
  • CD40 Deficiency
  • Activation-Induced Cytidine Deaminase (AID) Deficiency
  • Uracil-Nucleoside-Glycosylase (UNG) Deficiency
• Immunodeficiency–Centromeric Instability–Facial Anomalies (ICF) Syndrome: normal B-cell counts with agammaglobulinemia
• Jacobsen Syndrome (Hemizygous Deletion of Part of the Long Arm of Chromosome 11)
• Immunosuppression
  • Autologous Hematopoietic Stem Cell (HSCT) (Bone Marrow Transplant, BMT) (see Hematopoietic Stem Cell Transplant)
  • Azathioprine (Imuran) (see Azathioprine)
  • Belimumab (Benlysta) (See Belimumab): anti-B cell monoclonal antibody
  • Chemotherapy
  • Corticosteroids (see Corticosteroids)
    • Patients taking ≥12.5 mg prednisone for at least 1 year are at increased risk of hypogammaglobulinemia
    • Patients with hypogammaglobulinemia due to corticosteroid usually retain specific antibody responses: therefore, they are not usually candidates for immunoglobulin replacement therapy
  • Gold (see Gold)
  • Mycophenolate Mofetil (Cellcept) (see Mycophenolate Mofetil): may cause hypogammaglobulinemia
  • Rituximab (Rituxan) (see Rituximab)
  • Tyrosine Kinase Inhibitors
    • Dasatinib (Sprycel) (see Dasatinib)
    • Imatinib (Gleevec) (see Imatinib)
• Isolated IgA Deficiency (see Isolated IgA Deficiency): few reported cases of bronchiectasis (although these were probably due to undetected IgG deficiencies): most common primary immunodeficiency syndrome (occurs in 1:600 persons)
• Lymphoproliferative Malignancy
  • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia): commonly associated with hypogammaglobulinemia and infection
  • Multiple Myeloma (see Multiple Myeloma): antibody deficiency with normal total IgG levels (due to contribution of the paraprotein to the total IgG level and due to tumor cells altering normal regulatory T cells, impairing B-cell maturation)
• Myelodysplastic Syndrome (see Myelodysplastic Syndrome)
• Myotonic Dystrophy: increased catabolism of immunoglobulins
• Nephrotic Syndrome (see Nephrotic Syndrome)
  • Diagnosis
    • Hypoalbuminemia (see Hypoalbuminemia)
  • Clinical
    • Edema: usually
• Prematurity in Infants: premature infants delivered before the third trimester usually lack adequate maternal immunoglobulin and may also more rapid metabolize the IgG that they have received
• Protein-Losing Enteropathy: intestinal lymphangiectasia, etc
  • Diagnosis
    • IgG levels are typically affected more than IgM or IgA levels (however, the levels of IgG, IgM, and IgA may all be decreased in severe protein-losing enteropathy)
    • Hypoalbuminemia (see Hypoalbuminemia)
  • Clinical
    • Edema: usually
• Selective IgG Subclass Deficiency (see Selective IgG Subclass Deficiency): decrease in one or more of the four classes of IgG with normal total IgG is most common type associated with bronchiectasis
• Severe Burns (see Burns): increased catabolism of immunoglobulins
• Severe Combined Immunodeficiency (SCID) (see Severe Combined Immunodeficiency)
  • Epidemiology: xxx
• Specific Antibody Deficiency (SAD)/Specific Polysaccharide Antibody Deficiency (SPAD) (see Specific Antibody Deficiency): poor serological response to polysaccharide antigens (with normal levels of immunoglobulins and IgG subclasses) and normal responses to protein antigens
• Steinert’s Disease
• Transcobalamine Deficiency
• Trisomy 18
• Wiskott-Aldrich Syndrome

Other

• Chronic Granulomatous Disease (CGD) (see Chronic Granulomatous Disease)

Infection

• Adenovirus-Type 7 (see Adenovirus)
• Allergic Bronchopulmonary Aspergillosis (ABPA) (see Allergic Bronchopulmonary Aspergillosis)
  • Typically produces upper lobe bronchiectasis (mainly apical and posterior segments)
• Influenza Virus (see Influenza Virus)
  • Studies have shown transient nasal epithelial ciliary loss and dynein arm abnormalities in children during viral URI (influenza/ parainfluenza/ etc)
• Measles Virus (see Measles Virus)
• Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex)
• Mycobacterium Tuberculosis (see Tuberculosis)
  • Epidemiology: bronchiectasis may occur following primary tuberculosis or reactivation tuberculosis
  • Diagnosis: tuberculosis typically produces upper lobe bronchiectasis (mainly in the apical and posterior segments)
• Necrotizing Pneumonia and Pulmonary Gangrene (see Necrotizing Pneumonia and Pulmonary Gangrene)
• Pertussis (see Pertussis)
• Recurrent Aspiration Pneumonia (see Aspiration Pneumonia): bronchiectasis probably results from combined injury from infection and gastric acid

Inhalation Injury

• Ammonia Inhalation (see Ammonia)
• Sulfur Mustard Gas Inhalation (see Sulfur Mustard Gas)
• Smoke Inhalation (see Smoke Inhalation)
• Recurrent Aspiration Pneumonia (see Aspiration Pneumonia): bronchiectasis probably results from combined injury from infection and gastric acid

Other

• Alpha-1 Antitrypsin Deficiency (see Alpha-1 Antitrypsin Deficiency)
• Chronic Lung Transplant Rejection (see Lung Transplant)
• Congenital Bronchiectasis
• Cystic Fibrosis (CF) (see Cystic Fibrosis)
• Ehlers-Danlos Syndrome (see Ehlers-Danlos Syndrome)
• Inflammatory Bowel Disease (see Inflammatory Bowel Disease)
  • The Large Airways are the Most Common Site of Lung Involvement in Inflammatory Bowel Disease
    • Bronchiectasis is the Most Common Manifestation
  • Some cases (mostly ulcerative colitis) have recurrence of bronchiectasis after colectomy
• Localized Airway Obstruction
  • Airway Foreign Body (see Airway Foreign Body)
  • Endobronchial Tumors: bronchial adenoma, bronchial carcinoid, lung cancer, endrobronchial metastases, etc
  • Middle Lobe Syndrome (see Middle Lobe Syndrome)
• Marfan’s Syndrome (see Marfan Syndrome)
• Mounier-Kuhn Syndrome (see Mounier-Kuhn Syndrome): tracheobronchomegaly
• Peripheral Neuropathy (see Peripheral Neuropathy)
  • 2 cases had resolution of neuropathy with treatment of bronchiectasis
• Primary Ciliary Dyskinesia (see Primary Ciliary Dyskinesia)
• Pulmonary Sequestration (see Pulmonary Sequestration)
• Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis)
• Sarcoidosis (see Sarcoidosis)
• Scleroderma (see Scleroderma)
  • Epidemiology: cylindrical bronchiectasis is common in scleroderma
  • Physiology: due to recurrent aspiration or traction bronchiectasis associated with interstitial lung disease
• Swyer-James-Macleod Syndrome (see Swyer-James-Macleod Syndrome)
• Unilateral Pulmonary Artery Agenesis (see Unilateral Pulmonary Artery Agenesis)
• Williams-Campbell Syndrome (see Williams-Campbell Syndrome): congenital cartilage deficiency
• Yellow Nail Sydrome (see Yellow Nail Syndrome)

General Comments

• There is No Epidemiologic or Etiologic Significance to This Classification

Classification

• Cylindrical: consistent widening of segments
• Varicose: local constrictions in cylindrical segments (resembling varicose veins)
• Saccular/Cystic: dilatation increases toward lung periphery (forming sacs)

Arterial Blood Gas (ABG) (see Arterial Blood Gas)

• Mild Hypoxemia with Normocapnia/Hypocapnia: hypoxemia is due to intrapulmonary shunt and V/Q mismatch)
  • Hypercapnia: uncommon and is seen only in advanced cases or in those patients with superimposed COPD

Sputum Gram Stain and Culture

• Classic 3-Layered Sputum
  • Top: frothy watery layer
  • Middle: turbid mucopurulent layer
  • Bottom: purulent opaque layer (bottom layer may also contain Dittrich’s plugs and/or yellow or white concretions)
• Culture
  • Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa): colonizes bronchiectasis patients in 33% of cases
  • Haemophilus Influenzae (see Haemophilus Influenzae): common
  • Other Gram-Negatve Rods: common
  • Staphylococcus Aureus (see Staphylococcus Aureus): may be seen in some cases
  • Streptococcus Pneumoniae (see Streptococcus Pneumoniae): may be seen in some cases
  • Non-Tuberculous Mycobacteria: commonly cultured in North American patients
  • Mycobacterium Avium-Intracellulare (MAI) (see Mycobacterium Avium Complex): most common mycobacteria found in bronchiectasis patients
  • Mycobacterium Abscessus (see Mycobacterium Abscessus)

Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)

• Most Studies are Flawed, Since Concurrent Chronic Obstructive Pulmonary Disease (COPD) Cannot Be Excluded
  • However, Many Cases of Bronchiectasis Manifest Obstruction)
• Features
  • FEV1: usually decreased
  • FEF25-75: may be decreased:
  • Mild restriction: may be seen in some cases (especially if underlying disease decreases volumes)
  • DLCO: may be decreased

Bronchoscopy (see Bronchoscopy)

• Airways may appear wider on visual examination
• Useful to evaluate for sources of hemoptysis, rule out foreign bodies, etc.
• TBB: not usually performed

Chest X-Ray (CXR)/Chest CT Patterns (see xxxx and xxxx)

• Cylindrical: tram-tracks
• Varicose: toothpaste lines
• Cystic: cysts that may contain fluid

High-Resolution Chest CT (HRCT) (see High-Resolution Chest CT)

• Considered the gold standard imaging modality
• Sensitivity: 84%
• Specificty: 82%
• Bronchial wall thickening and dilatation

Bronchography

• No longer used

Serum Alpha-1 Antitrypsin (see Serum Alpha-1 Antitrypsin)

• To Rule out Alpha-1 Antitrypsin Deficiency (see Alpha-1 Antitrypsin Deficiency)

Immunoglobulin Levels (see xxxx)

• To rule out immunodeficiency

Sweat Chloride Test (see Sweat Chloride Test)

• To Rule Out Cystic Fibrosis (see Cystic Fibrosis)

Electron Microscopic Exam of Sperm or Respiratory Epithelium (Via Nasal Biopsy)

• To Rule Out Ciliary Disorder

Otolaryngologic Manifestations

Recurrent/Chronic Rhinosinusitis

• Epidemiology
  • Nasal/Sinus Disease May Be Seen in Association with Bronchiectasis Related to B-Cell Dysfunction Disorders

Pulmonary Manifestations

Chronic Hypoxemic, Hypercapnic Respiratory Failure (see Respiratory Failure)

• Epidemiology
  • Chronic Hypoventilation (Hypoxemic, Hypercapnic Respiratory Failure) Typically Occurs Only in Patients with Advanced Bronchiectasis or in Those with Superimposed Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)

Cough with/without Sputum Production (see Cough): most common symptom

• Clinical
  • “Wet Bronchiectasis”: purulent foul-smelling sputum
    • Mild: <10 mL per day
    • Moderate: 10-150 mL
    • Severe: >150 mL
  • “Dry Bronchiectasis”: some cases (especially those involving upper lobes that dependently drain) have minimal sputum

Dyspnea (see Dyspnea)

• Epidemiology
  • Dyspnea is More Common in Patients with Extensive Bronchiectasis and in Those with Superimposed Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)

Empyema (see Pleural Effusion-Parapneumonic)

• Epidemiology
  • XXXXX

Hemoptysis (see Hemoptysis)

• Epidemiology
  • More common in Dry Bronchiectasis
• Clinical
  • Usually Mild, But May Be Massive (>250 mL/Day)
  • Rarely Fatal

Lung Abcess (see Lung Abscess)

• xxx

Pneumothorax (see Pneumothorax)

• Epidemiology
  • XXXXX

Pulmonary Hypertension/Cor Pulmonale (see Pulmonary Hypertension)

• Epidemiology
  • Seen in some cases (37% of cases by 1969 study)
• Physiology
  • Enlargement of Bronchial Arteries: due to increased flow to tissue
  • Anastomoses to Pulmonary Arteries: due to enlargement of preexisting connections and new connections
  • Total Pulmonary Arterial Flow: may be decreased in severe bronchiectasis, due to obstructive endarteritis and/or hypoxic vasoconstriction
  • Left-to-Right Intrapulmonary Shunting Occurs: due to anastomoses

Rales/Rhonchi (see Pulmonary Physical Exam)

• xxx

Recurrent Pneumonia (see Community-Acquired Pneumonia)

• xxx

Wheezing (see Wheezing)

• xxxx

Rheumatologic Manifestations

Clubbing (see Clubbing)

• Physiology
  • Correlation between augmented vascular supply in lungs and vascularity in clubbed digits of bronchiectasis patients (suggests a possible vasodilator substance that is not yet identified)

Other Manifestations

• Amyloidosis (see Amyloidosis)
  • Rarely Seen Today in Developed Countries
• Brain Abscess (see Brain Abscess)
• Fever (see Fever)
• Generalized Weakness
• Weight Loss (see Weight Loss)