“High-Risk” Clinical and Inflammatory Clusters in COPD of Chinese Descent

Tiew, Pei Yee; Ko, Fanny Wai San; Narayana, Jayanth Kumar; Poh, Mau Ern; Xu, Huiying; Neo, Han Yee; Loh, Li‐Cher; Ong, Choo Khoon; Aogáin, Micheál Mac; Tan, Jessica; Kamaruddin, N.H.; Sim, Gerald Jiong Hui; Lapperre, Thérèse S.; Koh, Mariko Siyue; Hui, David Shu Cheong; Abisheganaden, John; Tee, Augustine; Tsaneva-Atanasova, Krasimira; Chotirmall, Sanjay H.

doi:10.1016/j.chest.2020.01.043

Cited by 14 publications

(14 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further validation of our findings in non-Asian populations would provide broader clinical relevance, and future work should include longitudinal assessments that incorporate air fungi from regions outside Singapore. In addition, characteristic of cohorts in the Asian setting, the majority of subjects in our studied cohort were male (>90%); however, it remains unclear whether this is due to lower rates of female smokers in the region or differing susceptibility to the development of COPD in Asian females [39].…”

Section: Discussionmentioning

confidence: 91%

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD

Tiew

Pang

et al. 2020

Eur Respir J

Self Cite

View full text Add to dashboard Cite

IntroductionAllergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis, however, clinical relevance in COPD remains unclear.MethodsPatients with stable COPD (n=446) and non-diseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assess outdoor and indoor environmental allergen exposure in COPD. We identify key fungi in outdoor air and develop specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of n=11 COPD patients and linked to clinical outcome.ResultsHigh frequencies of sensitisation to a broad range of allergens occurs in COPD. Fungal sensitisation associates with frequent exacerbations, and, unsupervised clustering reveals a “highly sensitised fungal predominant” sub-group demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD, and, promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function illustrating the importance of environmental exposures on clinical outcomes in COPD.ConclusionFungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in “sensitised” COPD.

show abstract

Section: Discussionmentioning

confidence: 91%

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD

Tiew

Pang

et al. 2020

Eur Respir J

Self Cite

View full text Add to dashboard Cite

show abstract

“…This may be, in part, due to the methods of identifying and categorizing comorbidities, as well as stringent recruitment criteria which may exclude patients with comorbidities. Some studies have used cluster analysis to analyze comorbidities; such analyses have been informative, 2 , 22 , 25 but these may not be feasible for smaller studies and lack broad applicability.…”

Section: Discussionmentioning

confidence: 99%

Impact of Comorbidity Prevalence and Cardiovascular Disease Status on the Efficacy and Safety of Nebulized Glycopyrrolate in Patients with COPD

Putcha¹,

Ozol-Godfrey²,

Sanjar³

et al. 2021

COPD

View full text Add to dashboard Cite

Purpose Patients with COPD often have multiple coexisting comorbidities, affecting quality of life, morbidity and mortality. However, the prevalence and impact of comorbidities on the efficacy of bronchodilators in COPD is poorly understood. Patients and Methods In this post hoc analysis, pooled data from the 12-week, placebo-controlled GOLDEN 3 and 4 studies of nebulized glycopyrrolate (GLY) in individuals with moderate-to-very-severe COPD were used to quantify comorbidities and assess their impact on treatment efficacy and safety. Results Comorbidities that were most prevalent in the GOLDEN 3 and 4 study population were hypertension, high cholesterol and osteoarthritis. Participants were grouped based on their pre-specified comorbidity count into Group A (≤2 comorbidities; n=439) and Group B (>2 comorbidities; n=854). Treatment with GLY resulted in significant improvements in forced expiratory volume in 1 second (FEV 1 ) and St George’s Respiratory Questionnaire (SGRQ) total scores, independent of comorbidity prevalence. A higher prevalence of cardiovascular disease (CVD) comorbidities was observed among individuals in Group B, compared with Group A. In a sub-analysis based on prevalence of CVD, treatment with GLY resulted in significant FEV 1 improvements independent of CVD prevalence, although values were numerically higher in the CVD group. GLY also led to higher improvements in SGRQ scores in the CVD group. GLY was well tolerated regardless of comorbidity or CVD prevalence, with a lower incidence of serious adverse events compared with placebo. Conclusion A simple comorbidity count demonstrated that a majority of patients with COPD in the GOLDEN 3 and 4 studies had multiple comorbidities, with CVD being common in those with high comorbidity count. Results from this post hoc analysis demonstrate that GLY improved FEV 1 and SGRQ scores in individuals with COPD, independent of their comorbidities or CVD status.

show abstract

“…The identification of specific clinically relevant disease endotypes has been greatly accelerated in respiratory medicine through the advent of systematic immunophenotyping studies [ 95 , 139 – 142 ]. Given the current revolution in monoclonal antibody therapies in clinical medicine, with many agents now licensed for therapy of asthma and allergic rhinitis, repurposing of these monoclonals for allergic fungal airway diseases in particular, and better understanding of which may be more efficacious in this setting, is a current high priority [ 143 , 144 ].…”

Section: How Can We Improve the Diagnosis Of Respiratory Fungal Infection?mentioning

confidence: 99%

Future Directions for Clinical Respiratory Fungal Research

Armstrong‐James

2021

Mycopathologia

View full text Add to dashboard Cite

There has been a growing appreciation of the importance of respiratory fungal diseases in recent years, with better understanding of their prevalence as well as their global distribution. In step with the greater awareness of these complex infections, we are currently poised to make major advances in the characterization and treatment of these fungal diseases, which in itself is largely a consequence of post-genomic technologies which have enabled rational drug development and a path towards personalized medicines. These advances are set against a backdrop of globalization and anthropogenic change, which have impacted the world-wide distribution of fungi and antifungal resistance, as well as our built environment. The current revolution in immunomodulatory therapies has led to a rapidly evolving population at-risk for respiratory fungal disease. Whilst challenges are considerable, perhaps the tools we now have to manage these infections are up to this challenge. There has been a welcome acceleration of the antifungal pipeline in recent years, with a number of new drug classes in clinical or pre-clinical development, as well as new focus on inhaled antifungal drug delivery. The “post-genomic” revolution has opened up metagenomic diagnostic approaches spanning host immunogenetics to the fungal mycobiome that have allowed better characterization of respiratory fungal disease endotypes. When these advances are considered together the key challenge is clear: to develop a personalized medicine framework to enable a rational therapeutic approach.

show abstract

“High-Risk” Clinical and Inflammatory Clusters in COPD of Chinese Descent

Cited by 14 publications

References 50 publications

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD

Environmental fungal sensitisation associates with poorer clinical outcomes in COPD

Impact of Comorbidity Prevalence and Cardiovascular Disease Status on the Efficacy and Safety of Nebulized Glycopyrrolate in Patients with COPD

Future Directions for Clinical Respiratory Fungal Research

Contact Info

Product

Resources

About