Impact of domestic mould exposure on Aspergillus biomarkers and lung function in patients with chronic obstructive pulmonary disease

Highlights

• Aspergillus is more frequent during AECOPD (16.9%) than at stable state (4.0%).

• Anti-Aspergillus antibodies frequency is similar during AECOPD and stable state.

• Anti-Aspergillus antibodies are associated with higher mould exposure during COPD.

• EDC mould counts >30 CFU/cm² can be used to define abnormal indoor contamination.

• Domestic mould exposure should be taken into account in COPD management.

Abstract

Patients with chronic obstructive pulmonary disease (COPD) are frequently colonised or sensitised by Aspergillus, but clinical significance remains unclear. Furthermore, little is known on the impact of indoor mould exposure during COPD. In this study, we assessed the relationship between domestic mould exposure, Aspergillus biomarkers and COPD severity during acute exacerbation and at stable state. Aspergillus section Fumigati culture in sputum and anti-Aspergillus antibodies detection (IgG and precipitins) were followed up in COPD patients that were prospectively recruited during exacerbation (n = 62), and underwent a visit at stable state after 18 months (n = 33). Clinical characteristics were collected at inclusion. Electrostatic dust collectors (EDCs) were used to measure domestic mould contamination. Aspergillus section Fumigati was more frequently detected during exacerbation (16.9%) than at stable state (4.0%), but the frequency of patients presenting with anti-Aspergillus antibodies was similar (32.2% and 33.3%, respectively). Aspergillus section Fumigati detection was associated with a higher body-mass index (BMI) during exacerbation, whereas patients with anti-Aspergillus antibodies presented a lower BMI and forced expiratory volume in 1 s, as well as a higher frequency of inhaled corticoids and higher total mould and Penicillium exposure at final visit (P < 0.05). The frequency of patients with anti-Aspergillus antibodies was higher for total mould counts >30 CFU/cm² (P = 0.03). Aspergillosis was diagnosed in 2 patients (6.1%) who presented increased levels of antibodies. Our data suggest that anti-Aspergillus antibodies are associated with chronic lung function alteration and/or domestic mould exposure, thereby supporting the consideration of indoor mould contamination and anti-Aspergillus antibodies kinetics in COPD management.

Introduction

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, which has a global mean prevalence of 12.4% in subjects aged ≥40 years in Europe (Blanco et al., 2018), and is mainly caused by inhalation of cigarette smoke. The hallmark feature of this disease is airflow limitation, but a substantial number of patients also suffer from acute exacerbations (AECOPD), which are a major cause of morbidity, mortality and hospital admission (Soler-Cataluña et al., 2005). AECOPD is mainly triggered by infections due to bacteria or viruses (Domenech et al., 2013), which have been shown to be facilitated by chronic inflammation and impaired lung immune defences (Le Rouzic et al., 2017; Pichavant et al., 2015, 2014). In addition, COPD patients are also at risk for invasive pulmonary aspergillosis (IPA). IPA has been increasingly reported with incidences varying from 1.6 to 3.9%, probably under-estimated, and is associated with a high mortality rate (72–100%) (Delsuc et al., 2015; Guinea et al., 2010).

Increasing evidence supports the role of filamentous fungi in stable COPD. Indeed, Aspergillus section Fumigati and anti-A. fumigatus antibodies are frequently detected in COPD patients at stable state (Agarwal et al., 2010; Bafadhel et al., 2014). Although patients with or without Aspergillus section Fumigati-positive culture show no difference in exacerbation frequency or respiratory function, Aspergillus sensitisation was found to be associated with a lower forced expiratory volume in 1 s (FEV1) (Bafadhel et al., 2014) or bronchiectasis (Everaerts et al., 2017). Indoor mould exposure, which is involved in the development and evolution of other respiratory diseases (Caillaud et al., 2018; French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 2016) could also play a role in the pathophysiology of COPD. However, little data is available to assess this possibility. One study evaluated fungal contamination using electrostatic dust fall collectors (EDCs) and showed no difference of fungal exposure between COPD patients and controls (Barrera et al., 2019). Nevertheless, another study has recently shown that indoor environments were associated with greater COPD symptoms and lower FEV1 at stable state (Tiew et al., 2020). The presence of indoor visible moulds was also identified as an independent risk factor of persistent bronchial obstruction (Ciebiada et al., 2014), and elevated indoor dust fungal DNA levels were found to be associated with low FEV1 or forced vital capacity in asthmatic patients (Shendell et al., 2012). Furthermore, visible moulds were found to be associated with FEV1 decrease in the general population (Devien et al., 2018). Altogether, these data suggest mould exposure could contribute to airflow limitation during COPD.

Here, our aim was to address the specific topic of mould exposure during COPD by using EDCs, which are innovative tools used to perform quantitative and qualitative characterisation of fungal flora (Ege et al., 2011; Dauchy et al., 2018; Viegas et al., 2019). We assessed the relationship between domestic mould exposure measured with EDCs, Aspergillus biomarkers (Aspergillus culture in sputum and anti-Aspergillus antibodies detection), and COPD severity (lung function and frequency of exacerbation episodes) in patients who were prospectively recruited during severe acute exacerbation requiring hospitalization, and underwent a final visit at stable state after 18 months.