Bronchodilator reversibility in patients with asthma and persistent airflow limitation – Authors' reply

Kole, Tessa; Kerstjens, Huib; Berge, Maarten van den

doi:10.1016/s2213-2600(22)00366-6

Cited by 3 publications

(4 citation statements)

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“…AO patients had a higher risk for having at least two exacerbations and more severe exacerbations in last year compared with COPD-only, and a borderline higher risk for having at least one exacerbation in last year compared with asthma-only. This is in line with a previous post hoc analysis of the ATLANTIS study, showing that AO patients had more exacerbations during 1 year of follow-up 41. Given the potential of unadjusted confounders such as medication use, this association should, however, be interpreted cautiously.…”

Section: Discussionsupporting

confidence: 90%

“…In addition to the differences in dyspnoea and FVC, AO patients from the general population had more frequently chronic bronchitis and showed more often elevated blood eosinophil levels, in line with a previous study on AO in a population of mild asthmatics 41. It cannot be ruled out, however, that AO patients may predominantly show mixed inflammation, as markers of neutrophilic inflammation were not collected in our study.…”

Section: Discussionsupporting

confidence: 85%

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Phenotyping asthma with airflow obstruction in middle-aged and older adults: a CADSET clinical research collaboration

Bertels,

Edris,

Garcia-Aymerich

et al. 2023

BMJ Open Resp Res

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BackgroundThe prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts.MethodsThis cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789). AO was defined as ever diagnosed asthma with pre-BD or post-BD FEV1/FVC <0.7 in population-based and clinic-based cohorts, respectively. Clinical characteristics and comorbidities of AO were compared with asthma without airflow obstruction (asthma-only) and chronic obstructive pulmonary disease (COPD) without asthma history (COPD-only). ORs for comorbidities adjusted for age, sex, smoking status and body mass index (BMI) were meta-analysed using a random effects model.ResultsThe prevalence of AO was 2.1% (95% CI 2.0% to 2.2%) in population-based, 21.1% (95% CI 18.6% to 23.8%) in asthma-based and 16.9% (95% CI 15.8% to 17.9%) in COPD-based cohorts. AO patients had more often clinically relevant dyspnoea (modified Medical Research Council score ≥2) than asthma-only (+14.4 and +14.7 percentage points) and COPD-only (+24.0 and +5.0 percentage points) in population-based and clinic-based cohorts, respectively. AO patients had more often elevated blood eosinophil counts (>300 cells/µL), although only significant in population-based cohorts. Compared with asthma-only, AO patients were more often men, current smokers, with a lower BMI, had less often obesity and had more often chronic bronchitis. Compared with COPD-only, AO patients were younger, less often current smokers and had less pack-years. In the general population, AO patients had a higher risk of coronary artery disease than asthma-only and COPD-only (OR=2.09 (95% CI 1.26 to 3.47) and OR=1.89 (95% CI 1.10 to 3.24), respectively) and of depression (OR=1.41 (95% CI 1.19 to 1.67)), osteoporosis (OR=2.30 (95% CI 1.43 to 3.72)) and gastro-oesophageal reflux disease (OR=1.68 (95% CI 1.06 to 2.68)) than COPD-only, independent of age, sex, smoking status and BMI.ConclusionsAO is a relatively prevalent respiratory phenotype associated with more dyspnoea and a higher risk of coronary artery disease and elevated blood eosinophil counts in the general population compared with both asthma-only and COPD-only.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 85%

Phenotyping asthma with airflow obstruction in middle-aged and older adults: a CADSET clinical research collaboration

Bertels,

Edris,

Garcia-Aymerich

et al. 2023

BMJ Open Resp Res

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“…Persistent airflow limitation (PAL) in asthma is defined as a post‐bronchodilator FEV 1 /forced vital capacity (FVC) less than the lower limit of normal at baseline, a condition representing a specific phenotype in asthmatic patients (GINA, 2023a; Kole et al, 2023). The bronchial tissue of asthmatic patients with PAL is characterised by inflammation and remodelling (Ferreira et al, 2018; Kozlik et al, 2020).…”

Section: In Vitro Studies With Isolated Airwaysmentioning

confidence: 99%

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

Calzetta,

Page,

Matera

et al. 2023

British J Pharmacology

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Isolated airway smooth muscle has been extensively investigated since 1840 to understand the pharmacology of airway diseases. There has been often poor predictability from murine experiments to drugs evaluated in patients with asthma or chronic obstructive pulmonary disease (COPD). However, the use of isolated human airways represents a sensible strategy to optimise the development of innovative molecules for the treatment of respiratory diseases. This review aims to provide updated evidence on the current uses of isolated human airways in validated in vitro methods to investigate drugs in development for the treatment of chronic obstructive respiratory disorders. This review also provides historical notes on the pioneering pharmacological research on isolated human airway tissues, the key differences between human and animal airways, as well as the pivotal differences between human medium bronchi and small airways. Experiments carried out with isolated human bronchial tissues in vitro and ex vivo replicate many of the main anatomical, pathophysiological, mechanical and immunological characteristics of patients with asthma or COPD. In vitro models of asthma and COPD using isolated human airways can provide information that is directly translatable into humans with obstructive lung diseases. Regardless of the technique used to investigate drugs for the treatment of chronic obstructive respiratory disorders (i.e. isolated organ bath systems, videomicroscopy, wire myography), the most limiting factors to produce high‐quality and repeatable data remain closely tied to the manual skills of the researcher conducting experiments and the availability of suitable tissue.

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“…Eosinophils exert an essential role in asthma, which associate with disease severity 138 . Eosinophils are the predominant cell types of necroptosis during asthma, which lead to airway hyperresponsiveness, inflammation, and remodeling 139 .…”

Section: The Key Molecular Mechanisms Underlying Necroptosis Of Speci...mentioning

confidence: 99%

Cell type‐specific molecular mechanisms and implications of necroptosis in inflammatory respiratory diseases

Guo,

Zhou,

Wang

et al. 2023

Immunological Reviews

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SummaryNecroptosis is generally considered as an inflammatory cell death form. The core regulators of necroptotic signaling are receptor‐interacting serine–threonine protein kinases 1 (RIPK1) and RIPK3, and the executioner, mixed lineage kinase domain‐like pseudokinase (MLKL). Evidence demonstrates that necroptosis contributes profoundly to inflammatory respiratory diseases that are common public health problem. Necroptosis occurs in nearly all pulmonary cell types in the settings of inflammatory respiratory diseases. The influence of necroptosis on cells varies depending upon the type of cells, tissues, organs, etc., which is an important factor to consider. Thus, in this review, we briefly summarize the current state of knowledge regarding the biology of necroptosis, and focus on the key molecular mechanisms that define the necroptosis status of specific cell types in inflammatory respiratory diseases. We also discuss the clinical potential of small molecular inhibitors of necroptosis in treating inflammatory respiratory diseases, and describe the pathological processes that engage cross talk between necroptosis and other cell death pathways in the context of respiratory inflammation. The rapid advancement of single‐cell technologies will help understand the key mechanisms underlying cell type‐specific necroptosis that are critical to effectively treat pathogenic lung infections and inflammatory respiratory diseases.

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Bronchodilator reversibility in patients with asthma and persistent airflow limitation – Authors' reply

Cited by 3 publications

References 1 publication

Phenotyping asthma with airflow obstruction in middle-aged and older adults: a CADSET clinical research collaboration

Phenotyping asthma with airflow obstruction in middle-aged and older adults: a CADSET clinical research collaboration

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

Cell type‐specific molecular mechanisms and implications of necroptosis in inflammatory respiratory diseases

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