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Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis - 29/11/24

Doi : 10.1016/S1473-3099(24)00567-X 
Abhinav Sengupta, MD a, , Animesh Ray, DM a, , , Ashish Datt Upadhyay, PhD b, Koichi Izumikawa, ProfMD PhD c, Masato Tashiro, MD PhD c, Yuya Kimura, MD d, e, Felix Bongomin, MMed f, Xin Su, ProfMD PhD g, Thomas Maitre, MD PhD h, Jacques Cadranel, ProfMD PhD h, Vitor Falcao de Oliveira, MD i, Nousheen Iqbal, FCPS j, k, Muhammad Irfan, ProfFCPS k, Yurdagül Uzunhan, MD PhD l, Juan Aguilar-Company, MD PhD m, Oxana Munteanu, MD PhD n, Justin Beardsley, MB BS PhD o, Koji Furuuchi, MD PhD p, Takahiro Takazono, MD PhD c, Akihiro Ito, MD q, Chris Kosmidis, MD PhD r, s, David W Denning, ProfFRCP s,
a Department of Medicine, All India Institute of Medical Sciences, New Delhi, India 
b Clinical Research Unit, All India Institute of Medical Sciences, New Delhi, India 
c Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan 
d Clinical Research Center, NHO Tokyo National Hospital, Tokyo, Japan 
e Department of Clinical Epidemiology and Health Economics, School of Public Health, University of Tokyo, Tokyo, Japan 
f Department of Medical Microbiology and Immunology, Faculty of Medicine, Gulu University, Gulu, Uganda 
g Department of Respiratory and Critical Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China 
h Service de Pneumologie et Oncologie Thoracique, National Reference Center for Rare Lung Disease, APHP Hôpital Tenon and Sorbonne Université and Cimi Paris, Inserm U1135, Paris, France 
i Department of Infectious Diseases, University of São Paulo, São Paulo, Brazil 
j Section of Pulmonary & Critical Care, Department of Medicine, Aga Khan University, Karachi, Pakistan 
k Jinnah Medical and Dental College, Karachi, Pakistan 
l Department of Respiratory Medicine, Reference Centre for Rare Pulmonary Diseases, APHP Hôpital Avicenne, Inserm U1272, Université Sorbonne Paris-Nord, Bobigny, France 
m Department of Medical Oncology and Department of Infectious Diseases, Vall d’Hebron Institute of Oncology, Vall d’Hebron Hospital Universitari, Barcelona, Spain 
n Department of Pneumology & Allergology, State University of Medicine and Pharmacy “Nicolae Testemitanu”, Medpark International Hospital, Chisinau, Moldova 
o Sydney Infectious Diseases Institute, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia 
p Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan 
q Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital, Kurashiki, Japan 
r National Aspergillosis Centre, Department of Infectious Diseases, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK 
s Manchester Fungal Infection Group, University of Manchester, Manchester, UK 

* Correspondence to: Dr Animesh Ray, Department of Medicine, All India Institute of Medical Sciences, New Delhi 110029, India Department of Medicine All India Institute of Medical Sciences New Delhi 110029 India ** Prof David W Denning, Manchester Fungal Infection Group, University of Manchester, Manchester M13 9NT, UK Manchester Fungal Infection Group University of Manchester Manchester M13 9NT UK
Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 29 November 2024

Summary

Background

Despite antifungal treatment, chronic pulmonary aspergillosis (CPA) is associated with substantial morbidity and mortality. We conducted a systematic review and meta-analysis to evaluate rates of mortality and its predictors in CPA.

Methods

A systematic literature search was conducted across MEDLINE (PubMed), Scopus, Embase, and Web of Science to identify studies in English, reporting mortality in CPA, from database inception to Aug 15, 2023. We included clinical studies, observational studies, controlled trials, and abstracts. Case reports, animal studies, letters, news, and literature reviews were excluded. Authors of studies published since 2016 were also contacted to obtain anonymised individual patient data (IPD); for other studies, summary estimates were extracted. Subgroup analysis was done for differences in overall 1-year and 5-year mortality, data source, study design, risk of bias, country, Human Development Index, age groups, and the underlying lung disease. We used random-effects meta-analyses to estimate pooled mortality rates. Subgroup analyses and meta-regression were done to explore sources of heterogeneity. One-stage meta-analysis with a stratified Cox proportional hazards model was used to estimate the univariable and hazards for mortality, adjusting for age, sex, type of CPA, treatment, and underlying pulmonary comorbidities. This study was registered with PROSPERO (CRD42023453447).

Findings

We included 79 studies involving 8778 patients in the overall pooled analysis and 15 studies involving 1859 patients in the IPD meta-analysis. Pooled mortality (from 70 studies) was estimated at 27% overall (95% CI 22–32; I2 =95·4%), 15% at 1 year (11–19; I2 =91·6%), and 32% at 5 years (25–39; I2 =94·3%). Overall mortality in patients with CPA with pulmonary tuberculosis as the predominant predisposing condition was 25% (16–35; I2 =87·5%; 20 studies) and with chronic obstructive pulmonary disease was 35% (22–49; I2 =89·7%; 14 studies). Mortality in cohorts of patients who underwent surgical resection was low at 3% (2–4). In the multivariable analysis, among predisposing respiratory conditions, pulmonary tuberculosis history had the lowest mortality hazard (relative to an absence of the disease at baseline), whereas worse outcomes were seen with underlying malignancy; subacute invasive pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis subtypes of CPA were also significantly associated with increased mortality relative to simple aspergilloma on multivariable analysis. Mortality hazard increased by 25% with each decade of age (adjusted hazard ratio 1·25 [95% CI 1·14–1·36], p<0·0001).

Interpretation

CPA is associated with substantial mortality. Advancing age, CPA subtype, and underlying comorbidities are important predictors of mortality. Future studies should focus on identifying appropriate treatment strategies tailored to different risk groups.

Funding

None.

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© 2024  The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Publié par Elsevier Masson SAS. Tous droits réservés.
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