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By Dr. Priyom Bose, Ph.D.Reviewed by Danielle Ellis, B.Sc.Dec 3 2024

Older age, specific disease subtypes, and underlying conditions like malignancy identified as major contributors to higher mortality risksStudy: Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis. Image Credit: Kateryna Kon/Shutterstock.com

Recently, scientists have systemically reviewed the available literature and conducted a meta-analysis to explore the reasons for high mortality rates associated with CPA despite the availability of antifungal treatments. This review is available in Lancet Infectious Diseases.

What is CPA?

CPA includes multiple lung diseases, such as chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA), caused by ubiquitous fungi of the genus Aspergillus. Individuals with modest immunocompromised conditions often develop subacute invasive pulmonary aspergillosis (SAIA). CPA has a slower disease course with high morbidity compared with pulmonary aspergillosis.

People with diabetes, tuberculosis, or low-dose systemic corticosteroid dependence are susceptible to CPA. A recent study revealed the possibility of an increase in CPA mortality by 20% in India. The annual incidence of CPA has been estimated to be 1.8 million cases with 3,04,000 deaths. In tuberculosis-endemic countries, CPAs are often misdiagnosed as sputum-negative pulmonary tuberculosis, which could be attributed to their increased prevalence cases and mortality rates.

Previous studies have documented significant variability in CPA mortality based on nomenclature, demographic background, region of publication, underlying pulmonary comorbidities, different management protocols, and the inequity of access to health care, among other factors. There is an urgent need to understand different aspects associated with CPA mortality to support clinical decisions for proper disease management that could effectively reduce mortality rates.

About the study

The current study conducted a systematic review and meta-analysis to evaluate the factors that influence CPA mortality rates and other aspects of the disease. All relevant CPA-related articles, including clinical studies, controlled trials, observational studies, and abstracts, were obtained from MEDLINE (PubMed), Scopus, Embase, and Web of Science databases from inception to August 15, 2023. However, animal studies, case reports, literature reviews, letters, and news articles were excluded.

Subgroup analyses were conducted to analyze the overall heterogeneity in 1-year and 5-year CPA mortality, and random-effects meta-analyses were conducted to estimate pooled mortality rates.

Study findings

This systematic review screened 1,452 citations, including 64 studies from 21 countries published between 1974 and 2023. The types of studies considered in this review included cross-sectional, case series, randomized controlled trials, cohort studies, and retrospective studies.

The sample size of the studies ranged between 10 and 1,705, which included a total of 8,778 CPA patients. The mean age of the patients ranged between 30 years and 79.1 years. The younger patients belonged to the WHO African region, and the older ones were from the Western Pacific region. Interestingly, the majority of CPA patients were identified as male.

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In comparison to Europe, a greater prevalence of post-tuberculosis lung disease has been documented in South-East Asia. However, chronic obstructive pulmonary disease (COPD) was found to be highest in European cohorts, followed by Western Pacific cohorts. A higher number of non-tuberculous mycobacterial lung disease cases has been reported from the Western Pacific region.

Among CPA patients, the most common underlying lung disease in the Southeast Asian and Western Pacific cohorts was post-tuberculosis lung disease, while COPD prevailed in European cohorts. A small number of studies reported the incidence of CPA subtypes, including CCPA (common), aspergilloma, SAIA, and CFPA (rare).

The cohort of individual patient data (IPD) included 1859 patients from the UK, Japan, and France. This cohort had a male dominance, with the mean age being 61.4 years. This cohort comprised CPA subtypes, including CCPA and SAIA. The median duration of follow-up was 616 days, which exhibited a 30% mortality rate in the cohort.

In the IPD cohort, a total of 676 patients were diagnosed with tuberculosis, whose mean age was 35.7 years. The majority of these patients had at least one underlying comorbidity. Diabetes, chronic corticosteroid use, radiotherapy, HIV infection, and chronic alcoholism were found to be the risk factors for patients with SAIA. Pulmonary tuberculosis, followed by COPD, was found to be a predisposing condition that leads to increased mortality rates in patients with CPA.

Although the majority of the IPD cohort received only oral or oral and intravenous antifungal agents, few received surgical interventions. In terms of antifungal agents, itraconazole was the most frequently used first-line treatment, followed by voriconazole.

Random-effects meta-analysis indicated 15% and 32% for 1-year and 5-year mortality, respectively. The incidence rate of mortality, estimated from 47 studies, was 104.5 deaths per 1000 person-years. The multivariable analysis indicated low mortality rates in patients who underwent surgical resection.

Conclusions

The current systematic review and meta-analysis revealed that CPA is associated with substantial mortality. CPA subtype, age, and underlying comorbidities were identified as the main factors that increased CPA mortality rates. Considering the study findings, novel treatment strategies tailored to different risk groups are needed, which could positively alleviate CPA mortality rates.

Journal reference:

• Sengupta, A. et al. (2024) Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis. The Lancet Infectious Diseases. doi.org/10.1016/S1473-3099(24)00567-X https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00567-X/fulltext?rss=yes