Radiological correlates and clinical implications of the paradoxical lung function response to β2 agonists: an observational study

Bhatt, Surya P.; Wells, James M.; Kim, Victor; Criner, Gerard J.; Hersh, Craig P.; Hardin, Megan; Bailey, William C.; Nath, Hrudaya; Kim, Young-il; Foreman, Marilyn G.; Stinson, Douglas; Wilson, Carla; Rennard, Stephen I.; Silverman, Edwin K.; Make, Barry J.; Dransfield, Mark T.

doi:10.1016/s2213-2600(14)70185-7

Cited by 23 publications

(29 citation statements)

References 32 publications

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“…In all participants, ΔFEV 1 and ΔFVC ranged from −20% to 27% (with a median value of 6.3%) and from −16% to 26% (with a median value of 3.8%), respectively. It is of note that two participants had a paradoxical response to the bronchodilator (≥12% and 0.2 L reduction in FEV 1 and FVC, respectively) 27 in terms of FVC fall, one participant in terms of FEV 1 fall, and one in terms of fall in both FEV 1 and FVC. As compared to Group 1, Group 2 showed significantly higher values for ΔFVC, but not for ΔFEV 1 ( Table 1 ).…”

Section: Resultsmentioning

confidence: 88%

“…Our result is in line with the findings of a recent study in >10,000 patients with COPD, which reported a paradoxical response to bronchodilators in nearly 5% of participants. 27 Compared with white patients, a paradoxical response was twice as common in African American patients (7% vs 3%). In the multivariate analyses, African American ethnic origin, less emphysema, airway wall thickness, worse dyspnea, reduced exercise capacity, and a greater frequency of exacerbations were independently associated with a paradoxical response.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

Pisi¹,

Aiello²,

Zanini³

et al. 2015

COPD

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BackgroundWe investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD).MethodsWe studied 100 (20 female; mean age: 68±10 years) patients with COPD (forced expiratory volume in 1 second [FEV1]: 55% pred ±21%; FEV1/forced vital capacity [FVC]: 53%±10%) by impulse oscillometry system. Resistance at 5 Hz and 20 Hz (R5 and R20, in kPa·s·L−1) and the fall in resistance from 5 Hz to 20 Hz (R5 – R20) were used as indices of total, proximal, and peripheral airway resistance; reactance at 5 Hz (X5, in kPa·s·L−1) was also measured. Significant response to bronchodilator (salbutamol 400 μg) was expressed as absolute (≥0.2 L) and percentage (≥12%) change relative to the prebronchodilator value of FEV1 (flow responders, FRs) and FVC (volume responders, VRs).ResultsEighty out of 100 participants had R5 – R20 >0.03 kPa·s·L−1 (> upper normal limit) and, compared to patients with R5 – R20 ≤0.030 kPa·s·L−1, showed a poorer health status, lower values of FEV1, FVC, FEV1/FVC, and X5, along with higher values of residual volume/total lung capacity and R5 (P<0.05 for all comparisons). Compared to the 69 nonresponders and the 8 FRs, the 16 VRs had significantly higher R5 and R5 – R20 values (P<0.05), lower X5 values (P<0.05), and greater airflow obstruction and lung hyperinflation.ConclusionThis study shows that peripheral airway resistance is increased in the vast majority of patients with COPD, who showed worse respiratory reactance, worse spirometry results, more severe lung hyperinflation, and poorer health status. Small airway dysfunction was also associated with the bronchodilator responsiveness in terms of FVC, but not in terms of FEV1.

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Section: Resultsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 96%

Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

Pisi¹,

Aiello²,

Zanini³

et al. 2015

COPD

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“…This significant reduction in lung function after the administration of a BD is termed paradoxical bronchoconstriction [32], and it has been previously reported to range between 0.5 and 1.5% according to the fixed and GLI-LLN cut-offs, respectively [33,34]. In another study, paradoxical responses were noted in 5% of the patients, and their frequency was similar in those with COPD and in smokers without AO [35]. This phenomenon was also independently associated with COPD intermediate endpoints, including reduced exercise capacity, increased dyspnoea and a greater frequency of exacerbations, and the authors assume it is an enigmatic COPD phenotype [35].…”

Section: Discussionmentioning

confidence: 99%

“…In another study, paradoxical responses were noted in 5% of the patients, and their frequency was similar in those with COPD and in smokers without AO [35]. This phenomenon was also independently associated with COPD intermediate endpoints, including reduced exercise capacity, increased dyspnoea and a greater frequency of exacerbations, and the authors assume it is an enigmatic COPD phenotype [35]. …”

Section: Discussionmentioning

confidence: 99%

The Prevalence of Chronic Obstructive Pulmonary Disease by the Global Lung Initiative Equations in North-Western Russia

et al. 2016

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Background: The prevalence of chronic obstructive pulmonary disease (COPD) varies in different countries, while the cut-off for airflow obstruction (AO) is still contested. No COPD prevalence data based on the Global Lung Initiative (GLI) 2012 equations are available in Russia. Objectives: This study aims to assess AO prevalence by the GLI lower limit of normal (GLI-LLN) and the fixed cut-off, to identify AO risk factors and to assess the diagnostic value of respiratory symptoms in north-western Russia. Methods: In a north-western Russian population-based sample of 2,974 adults aged 35-70 years, data on socio-demographics, smoking, occupational exposures and respiratory symptoms were collected, and spirometry was performed before and after bronchodilator (BD) administration. Results: The AO prevalence was 6.8% (95% CI 5.8-7.9) based on the fixed and 4.8% (95% CI 3.9-5.7) based on the GLI-LLN cut-off. 22.5% of the participants with post-BD AO had a positive bronchodilator test, and 1% showed a paradoxical BD response. Of the environmental factors studied, only smoking was independently associated with AO (odds ratio 2.47, 95% CI 1.60-3.82). The positive predictive value of respiratory symptoms for AO was 11% based on the fixed and 8% based on the GLI-LLN cut-off. Conclusions: In a sample of adults in north-western Russia, the AO prevalence by the GLI-LLN cut-off was lower than that by the fixed cut-off. The predictive value of respiratory symptoms was low.

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“…Despite this important clinical association of the ATS/ERS BDR criteria50 , when we excluded BDR positive participants by ATS/ERS criteria, we observed that clinical associations of BDR Grading Strategy persisted for 6MWD, SGRQ and mMRC in the adjusted multivariable analysis: patients with greater BDR had greater exercise performance, better quality of life and less dyspnea perception (Table 5).We observed that 21.1% of our study group had a negative response (defined as ≤0.00% or ≤0.00L FEV1 change) to albuterol. Recently, Bhatt and colleagues showed that a paradoxical response to beta-2 agonists resulting in bronchoconstriction was associated with respiratory morbidity measured by higher mMRC, frequent exacerbations and lower 6MWD52 . Probably, some of the participants in negative response category in our study can be regarded to have a paradoxical response to beta-2 agonists.…”

mentioning

confidence: 99%

A New Bronchodilator Response Grading Strategy Identifies Distinct Patient Populations

Hansen¹,

Dilektaşlı

Pórszász³

et al. 2019

Annals ATS

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Background: A positive bronchodilator response (BDR) by American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines requires an increase in FEV1 or FVC 200 mL and 12% after bronchodilator inhalation. This dual criterion is insensitive in those with high or low FEV1. We aimed to establish BDR criteria with volume or percentage FEV1 change. Methods: The largest FEV1 and FVC were identified from 3 pre-and 3 post-bronchodilator maneuvers in COPDGene participants. 7,741 individuals with coefficient of variation <15% for both FEV1 and FVC formed bronchodilator categories of FEV1 response: negative (≤0.00% or ≤0.00L), minimal (>0.00% to ≤9.00% or >0.00L to ≤0.09L), mild (>9.00% to ≤16.00% or >0.09L to ≤0.16L), moderate (>16.00% to ≤26.00% or >0.16L to ≤0.26L), and marked (>26.00% or >0.26L). These response-size categories are based on empirical limits considering average FEV1 increase of ~160 ml and the clinically important difference for FEV1. To compare flow and volume response characteristics, BDR-FEV1 category assignments were applied for the BDR-FVC response. Results: 20% met mild and 31% met moderate or marked BDR-FEV1 criteria; whereas 12% met mild and 33% met moderate or marked BDR-FVC criteria. In contrast, only 20.6% met ATS/ERS positive criteria. Minimal, mild, moderate and marked BDR-FEV1 categories were associated with greater six-minute walking distance, lower St. George's Respiratory Questionnaire and mMRC dyspnea scores as compared to those in negative BDR-FEV1 category. Moderate and marked BDR-FEV1 categories were associated with fewer exacerbations and minimal BDR was associated with lower computerized tomography airway wall thickness compared to negative BDR. Compared with negative, all BDR-FVC categories were associated 7 with increasing emphysema% and gas trapping%. Moderate and marked BDR-FVC categories were associated with higher SGRQ scores but fewer exacerbations and lower dyspnea scores. Conclusions: BDR grading by FEV1 volume or percentage response identified subjects otherwise missed by ATS/ERS criteria. BDR grades were associated with functional exercise performance, quality of life, exacerbation frequency, dyspnea and radiological airway measures. BDR grades in FEV1 and FVC indicate different clinical and radiological characteristics.

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Radiological correlates and clinical implications of the paradoxical lung function response to β2 agonists: an observational study

Cited by 23 publications

References 32 publications

Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

Small airway dysfunction and flow and volume bronchodilator responsiveness in patients with chronic obstructive pulmonary disease

The Prevalence of Chronic Obstructive Pulmonary Disease by the Global Lung Initiative Equations in North-Western Russia

A New Bronchodilator Response Grading Strategy Identifies Distinct Patient Populations

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