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Review 4: "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 onApr 25, 2024
Review 4: "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
Description

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.

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Review: In this preprint, the authors conducted a follow-up study to assess the incidence of CPA among pulmonary TB patients in India. It is a potentially informative study from an Indian setting. Though they mentioned several issues with the previous research work on this topic (as a rationale for the current study), the issues raised were not addressed properly in this current study and there are some methodological issues that need to be addressed.

  1. The authors should acknowledge the limitation of referral bias due to only recruiting patients presenting to a TB clinic. It should also be clarified how and what chronic lung conditions were ruled out. 

  2. Only Chest X-ray was done at baseline on all patients and similarly, not all patients underwent CT uniformly at the end of follow-up. Imaging is one of the important criteria for diagnosing CPA and hence, the chances of reporting bias must be acknowledged. 

  3. The factor loading done in the logistic regression must be revisited and must provide more details on the factors loaded and how the factors were selected and whether an adjusted analysis was carried out. Ultimately, the outcome measure must be in risk ratio/relative risk, not odds ratio.  

  4. Though CPA has a high case fatality rate, I am surprised by zero mortality among CPA cases in this cohort.

  5. The authors must clarify the role of the type of IgG kits used for negative Asp IgG among three patients with Aspergilloma. Can readers think of poor imaging or its reading/reporting?

  6. The authors must explain and discuss the reasons for higher SGRQ scores among CPA group compared to non-CPA group despite a high proportion with symptoms, imaging abnormality, anaemia, elevated CRP, etc.

  7. The authors must also clarify the testing and result of NTM among smear negative pulmonary TB.

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