Steroid insensitive fixed airflow obstruction is not related to airway inflammation in older non-smokers with asthma

Tonga, Katrina O.; King, Gregory G.; Farah, Claude S.; Thamrin, Cindy; Tang, Francesca; Santos, Jerran; Sharma, Pawan; Chapman, David G.; Oliver, Brian G.

doi:10.1186/s12931-018-0880-2

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…For instance, acute exacerbations are thought to be related to an acute inflammatory response owing to the increase in inflammatory markers preceding the exacerbation 24 and reductions in exacerbations after reductions in inflammatory cells. 25 However, previous studies by Tonga et al 6 suggest that FAO may relate to structural changes in the lung. In addition, the numbers in some of the groups were small and may have influenced the ability to observe a difference between omalizumab and placebo.…”

Section: Discussionmentioning

confidence: 97%

“…3,4 FAO in asthma develops over many years, resulting from airway inflammation and continued remodeling that results in thickening of the airway walls and parenchymal lung damage, leading to loss of elastic recoil. 5,6 These changes are associated with significant reductions in the size of the airway lumen and increased resistance to airflow. 5,6 Thickening of the airway walls is at least in part due to changes in the bronchial smooth muscle cells, including smooth muscle cell hypertrophy and hyperplasia, and increased deposition of extracellular matrix.…”

mentioning

confidence: 99%

“…5,6 These changes are associated with significant reductions in the size of the airway lumen and increased resistance to airflow. 5,6 Thickening of the airway walls is at least in part due to changes in the bronchial smooth muscle cells, including smooth muscle cell hypertrophy and hyperplasia, and increased deposition of extracellular matrix. [7][8][9] Early life factors, including in utero or postnatal viral infection and exposure to air pollution or tobacco smoking, are also believed to be important contributors to these airway structural changes.…”

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confidence: 99%

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Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA

Hanania

Fortis

Gupta³

et al. 2022

The Journal of Allergy and Clinical Immunology: In Practice

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What is already known about this topic? Fixed airflow obstruction in patients with asthma has been associated with reduced responsiveness to asthma medications.What does this article add to our knowledge? Omalizumab reduced exacerbations in patients with high bronchodilator reversibility and fixed airflow obstruction and improved lung function in patients without fixed airflow obstruction and high bronchodilator reversibility.How does this study impact current management guidelines? Identifying patient characteristics associated with improved outcomes with omalizumab may help to define patient populations that are more likely to derive benefit from omalizumab.BACKGROUND: Although asthma is typically characterized by bronchodilator responsiveness (BDR), fixed airflow obstruction (FAO) occurs in w50% of patients with severe asthma. OBJECTIVE: Do FAO/BDR associate with efficacy of omalizumab, a monoclonal antibody that targets IgE? METHODS: In EXTRA, patients aged 12-75 years with inadequately controlled severe allergic asthma despite high-dose inhaled corticosteroids plus long-acting b 2 -agonists were randomized to omalizumab (n [ 427) or placebo (n [ 423) for 48 weeks of treatment. In this post hoc analysis, high/low BDR were defined as ‡12%/<12% increases in baseline forced expiratory volume in 1 second (FEV 1 ) after bronchodilator administration, respectively. FAO presence (D)/absence (L) were defined as baseline postbronchodilator FEV 1 /forced vital capacity <70%/ ‡70%, respectively. Poisson regression/analysis of covariance models were used to estimate exacerbation relative rate reductions (RRRs)/least-squares mean changes in FEV 1 , respectively. RESULTS: In patients with high BDR, omalizumab reduced exacerbations more than placebo over the 48-week treatment period regardless of FAO status (RRR [95% confidence interval (CI)]: FAOD, 59. FAOL,). Omalizumab improved FEV 1 compared with placebo in the FAOL, high BDR subgroup (FEV 1 change from baseline [95% CI] for omalizumab vs placebo, 0.065 L [e0.071 to 0.201 L] to 0.236 L [0.112-0.359 L]) across 48 weeks. This was not observed in patients with low BDR, irrespective of FAO. CONCLUSION: Omalizumab was more efficacious than placebo at reducing exacerbations in patients with high, but not low, BDR, regardless of the presence of FAO. Lung function improvement primarily occurred in FAOL, high BDR patients, suggesting that

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

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confidence: 99%

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Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA

Hanania

Fortis

Gupta³

et al. 2022

The Journal of Allergy and Clinical Immunology: In Practice

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“…AO primarily affects severe asthma patients (40%–60% of severe asthmatics are estimated to have airway obstruction) and is more prevalent with older age 8 10–13. However, the prevalence and optimal treatment strategy of AO, including in AFO, have been a subject of debate 1.…”

Section: Introductionmentioning

confidence: 99%

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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“…Airflow limitation in asthma is commonly due to contraction of airway smooth muscle and structural changes such as increased thickness and fibrosis of the airway smooth muscle, which may cause irreversible obstruction 1 2 . Currently, the prevention and treatment of airflow limitation remains a challenge for clinicians 3 .…”

Section: Introductionmentioning

confidence: 99%

A comparative study of asthma with airflow limitation and asthma-COPD overlap using the forced oscillation technique

Sato

Tanaka

Hirai

et al. 2021

Showa Univ J Med Sci

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The forced oscillation technique FOT , which requires breathing without forced action, is a useful tool that can measure respiratory impedance. We investigated the physiological differences between asthma with smoking-unrelated airflow limitation and asthma-chronic obstructive pulmonary disease COPD overlap ACO using the FOT. Among 275 patients with asthma who presented at the Showa University Hospital from April 2018 through March 2019, 211 were enrolled and assigned into the asthma BA , asthma with airflow limitation AL , or ACO groups. Respiratory impedance measured using the FOT were compared among the groups. There were no significant differences in spirometry data between the AL and the ACO group. The AL group had higher respiratory resistance at 5 Hz R5 , 20 Hz R20 , and reactance at 5 Hz than the ACO group, but there was no significant difference in subtracting R20 from R5 R5-R20 . R5 and R20 were similar between the ACO and the BA groups, but R5-R20, resonant frequency Fres , and low-frequency reactance area were significantly higher in the ACO group than the BA group. Fres yielded the highest area under the curve AUC to identify airflow limitation, and R20 yielded the highest AUC to identify the ACO group among patients with airflow limitation. An analysis using the cut off value to identify airflow limitation and ACO detected 33 patients as having ACO, 17 of whom were diagnosed with ACO. R5 and R20 measured by FOT are higher in AL than in ACO despite no difference in spirometry data, and are not significantly different between BA and ACO. Therefore, FOT aids our understanding of the physiological characteristics and provides clues for the treatment in asthmatics with airflow limitation.

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Steroid insensitive fixed airflow obstruction is not related to airway inflammation in older non-smokers with asthma

Cited by 7 publications

References 13 publications

Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA

Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA

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

A comparative study of asthma with airflow limitation and asthma-COPD overlap using the forced oscillation technique

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