Distinct “Immunoallertypes” of Disease and High Frequencies of Sensitization in Non–Cystic Fibrosis Bronchiectasis

Abstract

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non-cystic fibrosis bronchiectasis remain unclear.Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immuneinflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined. Measurements and Main Results:A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome.Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.

The microbiome in bronchiectasis

“…The role of fungi, viruses and nontuberculous mycobacteria (NTMs) in bronchiectasis are less well defined, but are likely to be significant in bronchiectasis [28,61]. The CAMEB (Cohort of Asian and Matched European Bronchiectasis) study was the first to investigate the lung mycobiome in a cohort of 238 Asian and matched European bronchiectasis patients.…”

Bronchiectasis and cough: An old relationship in need of renewed attention

“…The primary clinical presentation of bronchiectasis includes chronic cough and recurrent respiratory infections responsible for the increased inflammation, airway damage and shortness of breath with eventual lung function decline, respiratory failure and death [1]. An increased awareness of disease heterogeneity, including its presence in overlap syndromes has brought renewed focus upon potential underlying molecular endophenotypes that may better define specific disease traits and subtypes amenable to treatment [2][3][4][5]. Endotypes represent disease presentations characterised by distinct functional or pathobiological mechanisms.…”

“…Effects were most pronounced in specific patient subgroupssuch as those colonised by basidiomycetous fungireinforcing the importance of microbiology and the targeted, personalised approach likely required. The potential application of antifungal therapeutics in bronchiectasis should however be targeted to specific disease subtypes, such as those driven by fungal allergy and, here, the identity of the inciting fungal species may be critically important [4,5,10,35,56].…”

“…The specific airway immune profile in bronchiectasis likely has direct consequences for cough hypersensitivity and cough phenotypes in bronchiectasis. Recently, our group has explored the role of sensitisation and allergy in bronchiectasis and identified high levels of atopic sensitisation, even in stable patients [5]. These observations have parallels with global atopic tendency in patients with chronic cough reflecting the central role of fungi and other allergens in allergic respiratory disease where cough is a predominant symptom [30] Importantly, our work also characterised the airway immune profile in bronchiectasis and revealed the existence of two distinct 'immuno-allertypes' defined by specific immune profiles.…”

Twenty‐five years of Respirology: Advances in bronchiectasis

“…High-quality translational research focused on the microbiome, immuno-inflammatory endo-phenotypes and identification of the 'frequent-exacerbator' phenotype all have the potential to improve future clinical trial outcomes by better selecting out 'responders' and choosing improved trial endpoints. 2,11,12 Significant ethno-geographic variation in aetiology, microbiology and clinical approach further poses a significant challenge to translating research findings into practice and, while severity scoring systems are established in adults, no validated biomarkers currently exist assessing disease severity, progression and/or exacerbations. Advances that have focused on neutrophil elastase activity and serum desmosine (including point-of-care testing for patient stratification) in bronchiectasis have shown promise.…”