COPD combine bronchiectasis: Double jeopardy of diseases

S5B – Pulmonary Infection
COPD COMBINE BRONCHIECTASIS: DOUBLE JEOPARDY OF DISEASES

Theerasuk Kawamatawong
Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

Background of diseases 
Bronchiectasis (BE) is chronic airway diseases that is characterized by chronic cough, sputum production and repeated respiratory infections. BE is a clinical and radiological diagnosis. According to the advantages of high-resolution computed tomography (HRCT) has been increasingly used in COPD assessment and allows for identifying bronchiectasis. Hence, the BE is frequently found in patients with COPD. Not only the overlapped clinical presentation between BE and COPD but also the co-existing COPD and the bronchiectasis has been observed in various stages of severity of COPD and increased the risk of COPD exacerbation. 

Definition 
The COPD is characterized by poorly reversible airflow obstruction. It is objectively diagnosed by functional measuring of airflow obstruction is associated with an abnormal inflammatory response of the lung to noxious stimuli and cigarette smoke.      The BE is structural diagnosis on thoracic imaging usually HRCT in the presence of permanent airway dilatation and airway wall thickening. Physiological diagnostic criteria for the COPD and radiological structural diagnostic criteria for the bronchiectasis have been well standardized. These criteria raise the diagnostic potential for either the co-morbidities and overlap syndrome between the bronchiectasis and COPD in clinical arena. 

Bronchiectasis and COPD 
The epidemiological studies shown that COPD having radiological proven bronchiectasis in the different magnitudes. Although, Global Initiative for Chronic Obstructive Lung Disease (GOLD) states that the bronchiectasis is both the differential diagnosis and COPD comorbidities. The presence of large volume and purulent sputum production with CT determined bronchial dilatation warrant the diagnosis of the bronchiectasis. The co-existing bronchiectasis with another airway diseases includes COPD are associated with increased airway inflammation, frequent exacerbations, accelerated lung function decline and increased mortality. 

The diagnosis of COPD combined with bronchiectasis and prevalence 
The coexistence of bronchiectasis and COPD is not uncommon. The prevalence that severe COPD have documented bronchiectasis ranges from 4% to 72%. The classical radiological criteria for the diagnosis of bronchiectasis are broncho-arterial (BA) ratio >1.0 with airway wall thickening on chest CT. Nevertheless, the hypoxic vasoconstriction secondary to airway diseases such as COPD may lead to either underdiagnosis or overdiagnosis of or bronchiectasis according to radiological bronchial dilatation criteria. Lastly, the one-fifth of healthy elderly subjects have BA ratio >1.0 without symptoms of bronchiectasis were observed. To date, there are the unmet needs regard to pathophysiology, epidemiology, natures of diseases and specific treatments for the patients with COPD combined with bronchiectasis. 

Lung imaging in COPD combined with bronchiectasis 
The globally increased utility of chest CT as part of the diagnosis and assessment of COPD patients consequently impacts on the detection of radiological airway wall changes. This approach results in diagnosed the bronchiectasis regardless of COPD severity. The mild and diffuse airway wall changes are commonly observed in COPD. However, localized or diffuse wall changes of airways and luminal dilatation in different severity including tubular, saccular or varicose and cystic bronchiectasis are common regardless of the bronchiectasis etiologies. 

Management of COPD combined with bronchiectasis
The essential etiological investigations of COPD combined with bronchiectasis are highly variable with healthcare resources. The α1-antitrypsin deficiency in bronchiectasis and early-onset COPD was recommended. Serum immunoglobulins assay is crucial for the assessment of bronchiectasis but not COPD. To determine whether a primary diagnosis is COPD or bronchiectasis according to clinical ground is challenging and difficult. COPD with secondary changes of bronchiectasis versus primary bronchiectasis with secondary fixed airflow limitation are commonly encountered entities and difficult clinical dilemma. 

The establishment of the primary diagnosis is crucial for the optimal management for COPD combined with bronchiectasis patients fulfilled both diagnoses criteria. The COPD as a primary diagnosis should be considered in tobacco smokers with persistent and progressive dyspnea without infection. Moreover, the presence of emphysema, and mild bronchiectasis all suggest that COPD is the primary clinical problem. In contrast to the bronchiectasis as a primary diagnosis should be considered in repeated infections and absence of risk or exposure to noxious particles and gases. Bronchodilators either LAMA or LABA are cornerstones in COPD treatments. However, they may not be effective in majority of patients with bronchiectasis. Inhaled corticosteroids (ICS)-containing regimens are widely used in COPD with frequent exacerbations but not recommended for most patients with bronchiectasis due to the diversity of etiologies. Nevertheless, inhaled or nebulized antibiotics including antipseudomonal coverage have been shown efficacy in bronchiectasis. They have been recommended for the bronchiectasis but are not used routinely in stable COPD treatment schema. 

Collectively, extrapolating this individual disease treatment to COPD combined bronchiectasis is limited. Hence management paradigms could greatly rely on the randomized control trial for this specific COPD phenotypes or overlap syndrome of two diseases. To date, there remain no definitive treatments for COPD combined bronchiectasis. The recommendation for diagnosis, evaluation and management for the COPD combined bronchiectasis is lack. 

References 
1. Polverino E, Soyza DA Dimakou K et al. The Association between Bronchiectasis and Chronic Obstructive Pulmonary Disease: Data from the European Bronchiectasis Registry (EMBARC) Am J Respir Crit Care Med. 2024; 1;210(1):119-127.
2. Sobala R, Soyza DA. Bronchiectasis and Chronic Obstructive Pulmonary Disease Overlap Syndrome. Clin Chest Med.  2022;43(1):61-70.
3. Polverino E, Dimakou K, Hurst J, et al. The overlap between bronchiectasis and chronic airway diseases: state of the art and future directions. Eur Respir J. 2018; 15;52(3)
4. Hurst JR, Elborn JS, De Soyza A, BRONCH-UK Consortium. COPD-bronchiectasis overlap syndrome. Eur Respir J.  2015;45(2):310-3.
5. Martinez-Garcia MA, Miravitlles M. Bronchiectasis in COPD patients: more than a comorbidity? Int J Chron Obstruct Pulmon Dis. 2017;12:1401–1411.
6. Matsuoka S, Uchiyama K, Shima H, et al. Bronchoarterial ratio and bronchial wall thickness on high-resolution CT in asymptomatic subjects: correlation with age and smoking. AJR Am J Roentgenol. 2003; 180: 513–518.
7. Kawamatawong T, Onnipa J, Suwatanapongched T. Relationship between the presence of bronchiectasis and acute exacerbation in Thai COPD patients. Int J Chron Obstruct Pulmon Dis. 2018; 2:13:761-769.
8. Ni Y, Shi G, Yu Y, Hao J, Chen T, Song H. Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015; 28:10:1465-75.
9. Ritchie A, Singayagam A, Mitchell S. Wedzicha JA, Shah A, Bloom C. The Effect of Inhaled Corticosteroids on Pneumonia Risk in Patients With COPD-Bronchiectasis Overlap: A UK Population-Based Case-Control Study. Chest. 2023;164(4):875-884
10. Chalmers JD, Shoemark A. Inhaled Corticosteroids in COPD and Bronchiectasis: Use Biomarkers Rather Than Disease Labels. Chest. 2023;164(4):809-811.