A.G. Mathioudakis comments: Chronic bronchitis: an objective diagnosis of exclusion

The authors of the above article published would like to thank A.G. Mathioudakis and co-workers for their interest and comments regarding our recently published article in the July issue of the European Respiratory Journal [1].

A.G. Mathioudakis and co-workers raise a concern regarding the term of “chronic bronchitis phenotype” and the actual diagnosis. They also comment that the phenotype could include patients with tuberculosis, lung cancer, asthma, bronchiectasis and heart failure, and that these diagnoses were not sufficiently investigated in our study. We agree with the position that the phenotype includes patients with other conditions and, in this way, the term was addressed in our study [1]. The self-reported comorbidity (asthma, tuberculosis and lung cancer) of the subjects with spirometric diagnosis of chronic obstructive pulmonary disease (COPD) is clearly shown in table 3 of our article (description of subjects with COPD, by chronic bronchitis) [1]. However, we think that the problem is that A.G. Mathioudakis and co-workers did not understand the type of study PLATINO (Proyecto Latinoamericano de Investigación en Obstrucción Pulmonar) is. This study is a well-known population-based study on COPD and not a study of a selected COPD population, so it is not possible to conduct additional analyses to rule out, for example, congestive heart failure in this type of study. In addition, we think that it is important to highlight the existing proposal for defining COPD phenotypes as “a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death).” This more focused definition allows classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes [2]. This definition is not restricted exclusively to selected COPD samples (there is no limit for its use in unselected populations), so it can also be used to study COPD phenotypes in a population-based sample and this is the case of our study. We presented the association of chronic bronchitis symptoms (a single attribute of the disease) in the PLATINO COPD population with the severity of airway obstruction, subjects’ perceptions of their general health status, physical activity limitation and exacerbations (relation to clinically meaningful outcomes).

A.G. Mathioudakis and co-workers also made a comment regarding the low prevalence of the chronic bronchitis phenotype and suggest that this could be associated with the use of post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio <0.70 to define COPD and the possible over-diagnosis of stage I COPD patients with low symptom prevalence. Unfortunately, it seems that A.G. Mathioudakis and co-workers have not reviewed the supplementary material of our study, which shows all analyses performed using the lower limit of normal (LLN) to define COPD [1]. Interestingly, supplemental tables 1 and 2 showed the parallel analysis using the LLN to define COPD, and the proportion of persons in both groups was quite similar to that found with the use of the fixed ratio [1]. Supplemental table 3 (description of subjects with COPD), and supplemental figures 1 and 2 (Global Initiative for Chronic Obstructive Lung Disease severity distribution of COPD subjects by chronic bronchitis and general health status assessed in COPD and non-COPD subjects, respectively) also showed the analyses using the LLN definition with similar findings [1].

Finally, we think that the data presented in our article helps to better understand the prevalence of the chronic bronchitis phenotype in an unselected COPD population using different criteria for defining COPD, and the association of this phenotype with some important outcomes (reduced pulmonary function, more respiratory symptoms and exacerbations, worse health status, and more physical activity limitation).

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