New world, old problems
How Big is the Problem?
Patients with cystic fibrosis (CF) aside, the incidence of bronchiectasis is hard to accurately determine because the disease is so heterogeneous. Bronchiectasis has many causes, differs wildly in severity and can only be definitively diagnosed using computed tomography (CT) imaging.Â
Experts agree that a large undiagnosed reservoir likely exists in people who carry a label of asthma or COPD as all three diseases may exhibit airflow limitation on spirometry. Recent estimates suggest the prevalence of bronchiectasis to be 139 per 100,000 people in the U.S. with higher prevalence in women and the elderly.2Â As our population lives longer and we perform more CT scans, the incidence of bronchiectasis will continue to rise.
Regardless of the specific cause of bronchiectasis, it is the result of a vicious cycle of events.Â A (usually unknown) patient-specific factor leads to impaired mucociliary clearance and retention of airway secretions, which compromises host defenses. This promotes bacterial persistence and chronic infection, which incites inflammation leading to airway injury and remodeling. Breaking this cycle has proved elusive for many decades.
Who Gets It?
Phenotyping patients with bronchiectasis into broad groups has emerged as a way to categorize the disease to deliver targeted, evidence-based therapeutics. Bronchiectasis patients require regular oversight from a pulmonologist to optimize mucus clearance from the lungs (airway clearance), manage inhaled agents and treat exacerbations.Â
Bronchiectasis should be suspected in people with recurrent chest infections or pneumonia and anyone with a chronic productive cough. Bronchiectasis shares many pathological features with asthma and chronic obstructive pulmonary disease (COPD). All three of these syndromes manifest persistent airway inflammation in response to different stimuli, however, the exaggerated neutrophilic response in bronchiectasis is what leads to unique airway destruction.Â
Roughly half the patients in the Bronchiectasis Registry have airway obstruction with a reduced FEV1 to FVC ratio on spirometry, and 60% have never smoked. Similarities between asthma, COPD and bronchiectasis frequently lead to diagnostic mistakes or delays in appropriate treatment.Â People with bronchiectasis typically suffer from fatigue, cough, sputum, hemoptysis and dyspnea with an average age of first diagnosis in the 50s3Â (U.S. data). Bronchiectasis should be suspected in anyone with recurrent respiratory infections, patients labeled as having COPD without a convincing tobacco history, and asthmatics who donâ€™t respond to typical therapies. Referral to a pulmonologist may allow for an accurate evaluation and an individualized management plan to be made.Â Â
Important Subgroups to ConsiderCystic Fibrosis
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) lead to altered epithelial ion transport from birth with severe bronchiectasis developing in childhood. The clinical severity varies depending on the type of CFTR mutation, as well as environmental or other factors.
The advent of newborn screening has had a huge impact on the early diagnosis of cystic fibrosis (CF). This is important because early detection of this disease confers a much better long-term outlook for people with CF.Â
Currently approximately 75% of people with CF are diagnosed in infancy.4Â That still leaves 25% of people with rarer CFTR mutations living into adulthood with chronic undiagnosed respiratory illnesses. Identifying adults with mild cystic fibrosis or a CFTR-related disorder (formally CF-variant) is crucial to provide access to a new generation of disease modifying therapies.Â
Once a fatal childhood illness, CF is transforming into a chronic illness with the majority of people living with CF being adults. This dramatic improvement in prognosis in CF has been the result of funding a new generation of small molecule drugs that overcome specific gene mutations and can essentially “switch off” CF for people who carry the most common CFTR mutations. Once a pipe dream, personalized medicine is now a reality for 90% of people with CF in the U.S.
Immunodeficiency. Defective host defenses may be characterized as local to the lung or systemic in nature. Regardless, a reliable association with the development of bronchiectasis is noted among susceptible individuals.Â Local immune deficiency can result from (1) ciliary dyskinesia, where failure of the mucociliary escalator leads to bacterial persistence and chronic inflammation, and (2) alpha-1 antitrypsin deficiency where unchecked neutrophil elastase activity in the lung leads to emphysema and bronchiectasis in people homozygous for the deficient or null gene alleles.Â
Systemic immunodeficiency is increasing in incidence. Biologic, disease-modifying drugs used in rheumatological and oncological disease predispose people to bronchiectasis through cellular and humoral changes at the airway mucosa, which promote bacterial persistence and chronic inflammation.Â
Hypogammaglobulinemia is another important cause of bronchiectasis. Patients treated for inflammatory bowel disease, inflammatory arthritis and other autoimmune diseases should be suspected to have bronchiectasis when compatible signs and symptoms are present.Â
Pulmonary Infections & Bronchiectasis
Respiratory infections are the largest cause of morbidity in bronchiectasis. Not only can severe infections cause localized bronchiectasis in many cases (for example tuberculosis, pneumococcal pneumonia, childhood bronchitis), but opportunistic infections in damaged airways accelerate lung function decline, exacerbate symptoms and are difficult to eradicate. Remodeled airways lack typical airway immunity and allow pathogens such as pseudomonas spp., burkholderia spp., acinetobacter spp. and mycobacteria to persist and colonize bronchiectatic lungs.Â
Chronic pseudomonas may develop a hardy biofilm impenetrable to antibiotics, and transitions to a â€œmucoidâ€ phenotype becomes virtually impossible to eradicate. Chronic pseudomonas infection is reliably associated with poorer short- and long-term outcomes for people with bronchiectasis. Therefore, delaying or preventing this complication is crucial.Â
Mycobacteria are ubiquitous organisms with the potential to cause insidious infections in human lungs. They may drive airway inflammation and destruction or worsen pre-existing bronchiectasis, leading to accelerated lung function loss, weight loss, chronic cough and dyspnea. The decision to treat positive mycobacterial cultures is carefully considered and individualized as treatment regimens are protracted and arduous to the patient.Â Â
What Treatments Help in Bronchiectasis?
The key to improving outcomes for patients with bronchiectasis is early detection, aggressive airway clearance and diligent surveillance for pulmonary infections. Airway clearance refers to a patient-specific regimen that promotes sputum expectoration. This is achieved using a combination of bronchodilators, mucolytics, breathing maneuvers, oscillating positive expiratory pressure therapies (â€œflutter valvesâ€) and high-frequency chest wall oscillation (â€œvest therapyâ€).Â
When performed effectively, airway clearance moves mucus from the small airways out of the lung. This has been shown to improve lung function and symptoms, reduce exacerbation frequency and delay acquisition of chronic opportunistic infections. Tailored airway clearance is the cornerstone of good bronchiectasis care.
Infection surveillance is the proactive collection and culture of patient sputum at every clinic visit. By identifying pathogens early, eradication of infections most prone to persist is possible. Furthermore, antibiotic directed therapy is possible in the event of a subsequent infectious exacerbation. The presence of environmental pathogens such as non-tuberculous mycobacteria do not automatically require treatment and must be interpreted in the context of the patientâ€™s symptoms, lung function stability and imaging studies.Â
What is My Role in This?
Bronchiectasis may complicate other diseases and confer significant morbidity on people afflicted by it. An increasingly aged and immunocompromised population will only increase the reservoir of undiagnosed bronchiectasis.Â
Especially in Georgia with its high rates of asthma, cystic fibrosis and COPD, we believe there are many undiagnosed people suffering with bronchiectasis. Medical providers should keep a high suspicion of the â€œgreat masqueraderâ€ when respiratory symptoms are not improving predictably with usual treatments. Identifying these patients early in their disease course improves their long-term prospects through access to disease-specific therapies, clinical trials and support groups.Â
1. Laennec R. A treatise on the diseases of the chest and on mediate auscultation. Paris: Samuel Wood and Sons; 1819. pp. 100â€“108.
2. Weycker D, Hansen GL, Seifer FD. Prevalence and incidence of noncystic fibrosis bronchiectasis among US adults in 2013. Chron Respir Dis. 2017 Nov;14(4):377-384. doi: 10.1177/1479972317709649. Epub 2017 May 30. PMID: 28555504; PMCID: PMC5729734.
3. Aksamit TR, O’Donnell AE, Barker A, Olivier KN, Winthrop KL, Daniels MLA, Johnson M, Eden E, Griffith D, Knowles M, Metersky M, Salathe M, Thomashow B, Tino G, Turino G, Carretta B, Daley CL; Bronchiectasis Research Registry Consortium. Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry. Chest. 2017 May;151(5):982-992. doi: 10.1016/j.chest.2016.10.055. Epub 2016 Nov 23. PMID: 27889361; PMCID: PMC6026266.
4. Cystic Fibrosis Foundation Patient Registry 2019 Annual Data Report Bethesda, Maryland Â©2020 Cystic Fibrosis Foundation