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Review 5: "Chronic Pulmonary Aspergillosis Incidence in Newly Detected Pulmonary Tuberculosis Cases during Follow-up"

Reviewers were mixed, with some finding the study well-written and important while others had concerns about generalizability, misclassification of CPA/TB, and interpretability of findings.

Published onMay 10, 2024
Review 5: "Chronic Pulmonary Aspergillosis Incidence in Newly Detected Pulmonary Tuberculosis Cases during Follow-up"
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key-enterThis Pub is a Review of
Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up
Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up

Abstract Background Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at end-of-therapy.Materials & Methods This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA.Results We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at end-of-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-therapy.Conclusions CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.


Review: This prospective study investigated the incidence of chronic pulmonary aspergillosis (CPA) among individuals newly diagnosed with pulmonary tuberculosis (P.TB), both at the beginning and at the conclusion of tuberculosis treatment. Out of 255 patients initially enrolled, 62% completed the follow-up period. The presence of Anti-Aspergillus IgG antibodies was detected in 11.1% of patients at baseline, which increased to 27.8% by the end of therapy. The study found that the confirmed diagnosis of CPA was made in 7% of patients at baseline and rose to 14.5% by the end of therapy.

My overall assessment is that this research focuses on a relevant topic and represents a novel contribution as there have been few studies addressing the incidence of CPA in newly diagnosed P.TB cases. The paper is well-written overall, and the authors demonstrate careful and thorough work. The data presentation is clear, though there is room for greater detail in certain aspects.

Specific Comments:

  1. Introduction/Aims:

    • The introduction effectively outlines the topic and the study's aim to analyze the relevant variables. However, refining the language could enhance reader comprehension. The terms like "burden" can lead to assumptions about the research question. It's crucial to clearly address the research question to establish a strong connection between the problem and the research objectives. Clarifying the research question will guide readers in understanding the study's purpose and goals more accurately.

  2. Methods:

    • In the method section, the study design hasn't been explicitly outlined. While the time, location, and criteria for selecting research subjects are mentioned, the author should explain how the data was obtained, whether through direct interviews with subjects, medical records review, or any other means.

    • Although the author mentioned clinical definitions, they need to be more detailed, especially regarding the symptoms and investigations related to classification of CPA.

    • In the results section, logistic regression results are presented, but it's not mentioned in the statistical analysis section. Including this information would provide a clearer understanding of the statistical methods used in the study.

  3. Key Findings:

    • Creating a patient flow diagram from recruitment to the end of the study would indeed be helpful for readers to better understand the study's progression. It provides a visual representation of how patients were enrolled, treated, and followed up, which can enhance clarity.

    • There is inconsistency in the abstract and result regarding the percentage of diagnosed proven CPA (14.5% vs. 15%), it's important for the authors to ensure accuracy and consistency in reporting results throughout the manuscript. Minor discrepancies like these can impact the credibility of the study.

  4. Significance:

    • The conclusion that CPA could coexist with or complicate newly diagnosed P.TB patients from diagnosis to the end of therapy underscores the importance of early detection and its diagnostic challenges.

    • However, it's worth noting that this study specifically aims to analyze CPA incidence in newly detected P.TB cases, and it does not delve into the discussion of CPA incidence in sputum-negative P.TB cases, possible or probable CPA, the potential for misdiagnosis, or its differential diagnosis. Including this discussion would enhance the understanding of the study's relevance and clarify the importance of recognizing potential diagnostic challenges and differentiating between these conditions effectively.

I would recommend that the authors:

  • Clearly state the research question to enhance understanding of the study's purpose and objectives

  • Specify methodological details like study design, data collection methods, clinical definitions, and analytical approaches

  • Explore the potential for misdiagnosis and differential diagnosis and their implications for diagnosis

  • Consider broadening the study scope by adding variables or including clinical definitions of probable or possible CPA to deepen understanding of CPA incidence in P.TB, and incorporating additional analyses like post hoc analysis.

The authors have undertaken valuable research on CPA incidence among individuals newly diagnosed with P.TB.  Although some sections require improvement and further elaboration, this manuscript offers coexistence and complications of CPA in newly diagnosed PTB and its diagnostic challenges. Therefore, we would like to suggest a major revision.

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