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]
Etiology
Idiopathic
Over 50% of All Bronchiectasis Cases are Idiopathic
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
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)
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
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)
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
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
Destruction of muscular and elastic components of medium-sized bronchial walls by mediators released by neutrophils (elastase) and monocytes (cytokines) -> >2 mm dilatation of medium-sized bronchi
Damage to peribronchial alveolar tissue: diffuse peribronchial fibrosis, squamous metaplasia of bronchial epithelium, and obliteration of distal bronchi and bronchioles
Impaired tracheobronchial clearance of secretions (shown by radiolabelled aerosol studies): predisposes to bacterial airway colonization and infection
Specific Role of Infection
It is not clear whether mycobacterial infection is a cause or a consequence of bronchiectasis [MEDLINE]
Pseudomonas infection appears to be asscoiated with more severe disease and cystic bronchiectasis
Mycobacterium Avium-Intracellulare (MAI) infection appears to be associated with nodular bronchiectasis (especially in the right middle lobe and lingula), mucous plugging of airways, and “tree in bud” small airway impaction
Reversibility of Bronchiectasis
May resolve after even years of observation in some cases (especially in areas of atelectasis due to previous pneumonia), although generally is believed to be permanent
Location
Can be diffuse or localized
Posterior-basal segments: most commonly involved
Bilateral LL involvement occurs in 33% of cases/ unilat-eral LL involvement occurs in left and right lungs with equal frequency/ 50% of patients with LLL involvement also have lingular involvement
RML is more commonly affected than RUL
UL involvement most common in posterior and apical segments (and is usually due to Allergic Bronchopulmonary Aspergillosis and Tuberculosis) (see xxxx and xxxx)
Pathologic Classification (Reid)
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)
Electron Microscopic Exam of Sperm or Respiratory Epithelium (Via Nasal Biopsy)
To Rule Out Ciliary Disorder
Clinical Manifestations
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
Dyspnea is More Common in Patients with Extensive Bronchiectasis and in Those with Superimposed Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
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)
Indications: localized bronchiectasis with recurrent infection unresponsive to antibiotics
Mucolytics
Agents
Coughing is Probably Superior
Agents
Deoxyribonuclease (DNase) (see Dornase Alfa): useful only for cystic fibrosis, as trials suggest that it has potential harmful effects in non-cystic bronchiectasis (Cochrane Database Syst Rev, 2014) [MEDLINE]
Bromhexine with Antibiotics: may facilitate sputum production and clearance, but long-term data and clinical outcomes are lacking
Erdosteine: may be a useful adjunct to physical therapy in stable patients with mucus hypersecretion, but robust longer-term trials are required
N-Acetylcysteine (Mucomyst) (see N-Acetylcysteine): further studies are required
Clinical Efficacy
xxxxx
Antibiotics
Clinical Utility
Antibiotic Treatment of Acute Exacerbation: antibiotics are standard therapy
Antibiotic Maintenance Therapy: indicated for patients with >2-3 exacerbations per year
During course of therapy, fluoroquinolones decrease sputum elastase, neutrophil chemotactic activity, sputum volume and purulence: however, 25% of patients relapse within 6 wks after therapy
Randomized Trial of Nebulized Gentamicin in Non-Cystic Bronchiectasis (Am J Respir Crit Care Med, 2011 ) [MEDLINE]
Regular long-term nebulized gentamicin 80 mg BID decreased sputum bacterial density, airway inflammation, and exacerbations (with no change in FEV1 or FVC)
Treatment needs to be continuous for ongoing efficacy
Systematic Review and Meta-Analysis of Inhaled Antibiotics in Bronchiectasis in Adults (Lancet Respir Med, 2019) [MEDLINE]: n = 2,597 (16 trials)
Inhaled antibiotics are well tolerated, reduce bacterial load, and achieve a small but statistically significant reduction in exacerbation frequency without clinically significant improvements in quality of life in patients with bronchiectasis and chronic respiratory tract infections
Systematic Review and Meta-Analysis of Inhaled Antibiotics in Bronchiectasis in Adults (Lancet Respir Med, 2019) [MEDLINE]: n = 2,597 (16 trials)
Inhaled antibiotics are well tolerated, reduce bacterial load, and achieve a small but statistically significant reduction in exacerbation frequency without clinically significant improvements in quality of life in patients with bronchiectasis and chronic respiratory tract infections
The mean reduction of colony forming units per g of sputum with inhaled antibiotics was -2·32 log units (95% CI -3·20 to -1·45; p<0·0001). Bacterial eradication was increased with inhaled antibiotic therapy (odds ratio [OR] 3·36, 1·63 to 6·91; p=0·0010). Inhaled antibiotics significantly reduced exacerbation frequency (rate ratio 0·81, 0·67 to 0·97; p=0·020). Time to first exacerbation was significantly prolonged with inhaled antibiotics (hazard ratio 0·83, 0·69 to 0·99; p=0·028). The proportion of patients with at least one exacerbation decreased (risk ratio 0·85, 0·74 to 0·97; p=0·015). There was a significant reduction in the frequency of severe exacerbations (rate ratio 0·43, 0·24 to 0·78; p=0·0050). The scores for neither the Quality of Life Bronchiectasis questionnaire nor St George’s Respiratory Questionnaire improved above the minimal clinically important difference. The relative change in FEV1 was a deterioration of 0·87% predicted value (-2·00 to 0·26%; p=0·13). Other efficacy endpoints were reported in only few studies or had few events. There was no difference in treatment-emergent adverse effects (OR 0·97, 0·67 to 1·40; p=0·85) or bronchospasm (0·99, 0·66 to 1·48; p=0·95). Emergence of bacterial resistance was evident at the end of the treatment period (risk ratio 1·91, 1·46 to 2·49; p<0·0001).
Azithromycin x 6 mo -> decreased rate of exacerbations (in patients who had at least one exacerbation in the past year)
BAT Trial (JAMA, 2013) [MEDLINE]: multi-center Dutch placebo-controlled study (n = 83) in non-cystic fibrosis bronchiectasis using daily azithromycin x 12 mo
Decreased rate of infectious exacerbations, increased rate of macrolide resistance
BLESS Trial (JAMA, 2013) [MEDLINE]: single-center Australian placebo-controlled study (n = 117) in non-cystic fibrosis bronchiectasis using daily erythromycin x 12 mo
Modest decrease in the rate of exacerbations, increased rate of macrolide resistance, decreased sputum production
Analysis of BLESS Trial Data (Lancet Respir Med, 2014) [MEDLINE]
Long-term erythromycin treatment changes the composition of respiratory microbiota in patients with bronchiectasis
In patients without Pseudomonas Aeruginosa airway infection, erythromycin did not significantly reduce exacerbations and promoted displacement of Haemophilus Influenzae by more macrolide-tolerant pathogens (including Pseudomonas Aeruginosa) -> these findings argue for a cautious approach to chronic macrolide use in patients without Pseudomonas Aeruginosa airway infection
Meta-Analysis of Long-Term Macrolides in Bronchiectasis in Adults (Lancet Resp Med, 2019) [MEDLINE]
Long-term macrolide treatment significantly reduces the frequency of exacerbations in patients with bronchiectasis, with similar benefits observed in all subgroups based on patient characteristics
This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful
However, downsides of long-term macrolide treatment must also be taken into account
Of 234 identified studies, we included three randomised controlled trials, and IPD was obtained for 341 participants. Macrolide antibiotics reduced the frequency of exacerbations (adjusted incidence rate ratio [IRR] 0·49, 95% CI 0·36 to 0·66; p<0·0001). We also found that macrolide treatment improved the time to first exacerbation (adjusted hazard ratio 0·46, 0·34 to 0·61; p<0·0001) and was associated with improved quality of life measured by the SGRQ (mean improvement 2·93 points, 0·03 to 5·83; p=0·048). Macrolides were not associated with a significant improvement in FEV1 (67 mL at 1 year, -22 to 112; p=0·14). Effect estimates in prespecified subgroup analyses revealed a reduced frequency of exacerbations in all prespecified subgroups, including a high level of benefit in patients with P aeruginosa infection (IRR 0·36, 0·18-0·72; p=0·0044) and in patients with one to two exacerbations per year (0·37, 0·16-0·88; p=0·025). Studies were rated as low risk of bias across all domains.
Prognostic Value of Bronchiectasis in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2013 Apr 15;187(8):823-31 [MEDLINE]
Treatment
A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med 2011;183:491-499 [MEDLINE]
Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):660-7 [MEDLINE]
Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA. 2013 Mar 27;309(12):1260-7 [MEDLINE]
Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013 Mar 27;309(12):1251-9 [MEDLINE]
The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial. Lancet Respir Med. 2014 Dec;2(12):988-96. doi: 10.1016/S2213-2600(14)70213-9. Epub 2014 Oct 14 [MEDLINE]
Mucolytics for bronchiectasis. Cochrane Database Syst Rev. 2014 May 2;5:CD001289. doi: 10.1002/14651858.CD001289.pub2 [MEDLINE]
Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis. Lancet Respir Med. 2019 Oct;7(10):845-854. doi: 10.1016/S2213-2600(19)30191-2 [MEDLINE]
The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: a systematic review and meta-analysis. Lancet Respir Med. 2019 Oct;7(10):855-869. doi: 10.1016/S2213-2600(19)30185-7 [MEDLINE]