Dataset Information

Mechanisms affecting exercise ventilatory inefficiency-airflow obstruction relationship in male patients with chronic obstructive pulmonary disease.

ABSTRACT:

Background

Exercise ventilatory inefficiency is usually defined as high ventilation ([Formula: see text]) versus low CO₂ output ([Formula: see text]). The inefficiency may be lowered when airflow obstruction is severe because [Formula: see text] cannot be adequately increased in response to exercise. However, the ventilatory inefficiency-airflow obstruction relationship differs to a varying degree. This has been hypothesized to be affected by increased dead space fraction of tidal volume (V_D/V_T), acidity, hypoxemia, and hypercapnia.

Methods

A total of 120 male patients with chronic obstructive pulmonary disease were enrolled. Lung function and incremental exercise tests were conducted, and [Formula: see text] versus [Formula: see text] slope ([Formula: see text]) and intercept ([Formula: see text]) were obtained by linear regression. Arterial blood gas analysis was also performed in 47 of the participants during exercise tests. V_D/V_T and lactate level were measured.

Results

V_D/V_Tpeak was moderately positively related to [Formula: see text] (r =?0.41) and negatively related to forced expired volume in 1 sec % predicted (FEV₁%) (r =?-?0.27), and hence the FEV₁%- [Formula: see text] relationship was paradoxical. The higher the [Formula: see text], the higher the pH and P_aO₂, and the lower the P_aCO₂ and exercise capacity. [Formula: see text] was marginally related to V_D/V_Trest. The higher the [Formula: see text], the higher the inspiratory airflow, work rate, and end-tidal PCO_2peak.

Conclusion

1) Dead space ventilation perturbs the airflow- [Formula: see text] relationship, 2) increasing ventilation thereby increases [Formula: see text] to maintain biological homeostasis, and 3) the physiology- [Formula: see text]- [Formula: see text] relationships are inconsistent in the current and previous studies.

Trial registration

MOST 106-2314-B-040-025 .

SUBMITTER: Chuang ML

PROVIDER: S-EPMC7409645 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Mechanisms affecting exercise ventilatory inefficiency-airflow obstruction relationship in male patients with chronic obstructive pulmonary disease.

Chuang Ming-Lung ML

Respiratory research 20200806 1

<h4>Background</h4>Exercise ventilatory inefficiency is usually defined as high ventilation ([Formula: see text]) versus low CO<sub>2</sub> output ([Formula: see text]). The inefficiency may be lowered when airflow obstruction is severe because [Formula: see text] cannot be adequately increased in response to exercise. However, the ventilatory inefficiency-airflow obstruction relationship differs to a varying degree. This has been hypothesized to be affected by increased dead space fraction of t ...[more]

PMID: 32762752

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Project description:BackgroundVentilatory inefficiency contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). The intercept of the minute ventilation (V˙ E) vs. carbon dioxide output (V˙ CO2) plot is a key ventilatory inefficiency parameter. However, its relationships with lung hyperinflation (LH) and airflow limitation are not known. This study aimed to evaluate correlations between the V˙ E/V˙ CO2 intercept and LH and airflow limitation to determine its physiological interpretation as an index of functional impairment in COPD.MethodsWe conducted a retrospective analysis of data from 53 COPD patients and 14 healthy controls who performed incremental cardiopulmonary exercise tests (CPETs) and resting pulmonary function assessment. Ventilatory inefficiency was represented by parameters reflecting the V˙ E/V˙ CO2 nadir and slope (linear region) and the intercept of V˙ E/V˙ CO2 plot. Their correlations with measures of LH and airflow limitation were evaluated.ResultsCompared to control, the slope (30.58±3.62, P<0.001) and intercept (4.85±1.11 L/min, P<0.05) were higher in COPDstages1-2, leading to a higher nadir (31.47±4.47, P<0.01). Despite an even higher intercept in COPDstages3-4 (7.16±1.41, P<0.001), the slope diminished with disease progression (from 30.58±3.62 in COPDstages1-2 to 26.84±4.96 in COPDstages3-4, P<0.01). There was no difference in nadir among COPD groups and higher intercepts across all stages. The intercept was correlated with peak V˙ E/maximal voluntary ventilation (MVV) (r=0.489, P<0.001) and peak V˙ O2/Watt (r=0.354, P=0.003). The intercept was positively correlated with residual volume (RV) % predicted (r=0.571, P<0.001), RV/total lung capacity (TLC) (r=0.588, P<0.001), peak tidal volume (VT)/FEV1 (r=0.482, P<0.001) and negatively correlated with rest inspiratory capacity (IC)/TLC (r=-0.574, P<0.001), peak VT/TLC (r=-0.585, P<0.001), airflow limitation forced expiratory volume in 1 s (FEV1) % predicted (r=-0.606, P<0.001), and FEV1/forced vital capacity (FVC) (r=-0.629, P<0.001).ConclusionsV˙ E/V˙ CO2 intercept was consistently correlated with worsening static and dynamic LH, pulmonary gas exchange, and airflow limitation in COPD. The V˙ E/V˙ CO2 intercept emerged as a useful index of ventilatory inefficiency in COPD patients.

Project description:ObjectivesTo determine the correlation between CT measurements of emphysema or peripheral airways and airflow obstruction in chronic obstructive pulmonary disease (COPD).MethodsPubMed, Embase and Web of Knowledge were searched from 1976 to 2011. Two reviewers independently screened 1,763 citations to identify articles that correlated CT measurements to airflow obstruction parameters of the pulmonary function test in COPD patients, rated study quality and extracted information. Three CT measurements were accessed: lung attenuation area percentage?<?-950 Hounsfield units, mean lung density and airway wall area percentage. Two airflow obstruction parameters were accessed: forced expiratory volume in the first second as percentage from predicted (FEV(1) %pred) and FEV(1) divided by the forced volume vital capacity.ResultsSeventy-nine articles (9,559 participants) were included in the systematic review, demonstrating different methodologies, measurements and CT airflow obstruction correlations. There were 15 high-quality articles (2,095 participants) in the meta-analysis. The absolute pooled correlation coefficients ranged from 0.48 (95 % CI, 0.40 to 0.54) to 0.65 (0.58 to 0.71) for inspiratory CT and 0.64 (0.53 to 0.72) to 0.73 (0.63 to 0.80) for expiratory CT.ConclusionsCT measurements of emphysema or peripheral airways are significantly related to airflow obstruction in COPD patients. CT provides a morphological method to investigate airway obstruction in COPD.Key points• Computed tomography is widely performed in patients with chronic obstructive pulmonary disease (COPD) • CT provides quantitative morphological methods to investigate airflow obstruction in COPD • CT measurements correlate significantly with the degree of airflow obstruction in COPD • Expiratory CT measurements correlate more strongly with airflow obstruction than inspiratory CT • Low-dose CT decreases the radiation dose for diagnosis and quantitative emphysema evaluation.

Project description:OBJECTIVES:Subglottic stenosis (SGS) is one of the most common airway disorders in pediatric patients. Currently, treatment decisions rely primarily on the Cotton-Myer scale, which classifies SGS severity based on percentage reduction in airspace cross-sectional area (CSA). However, the precise relationship between upper airway resistance and subglottic CSA is unknown. We hypothesize that airway resistance can be described by the Bernoulli Obstruction Theory, which predicts that airway resistance is inversely proportional to airspace CSA ( R∝A-1) in cases of severe constriction. METHODS:Computed tomography (CT) scans of six healthy subjects and five SGS patients were used to create three-dimensional models of the respiratory tract from nostrils to carina. Cylindrical segments of varying lengths and varying diameters were digitally inserted in the subglottis of the healthy subjects to create simulated SGS models. Computational fluid dynamics simulations were run, and airway resistance was computed in the simulated SGS models and actual SGS models. RESULTS:Constriction diameter had a greater impact in airway resistance than constriction length. In agreement with the Bernoulli Obstruction Theory, airway resistance in the simulated SGS models was well represented by the power law R=aAb, where a is a constant and the exponent b ranged from -0.85 to -1.07. The percentage reduction in airflow (QOBSTRUCTIONQHEALTHY) at a constant pressure drop was found to be directly proportional to the percentage reduction in CSA (AOBSTRUCTIONAHEALTHY) in the limit of severe constrictions, namely QOBSTRUCTIONQHEALTHY=kAOBSTRUCTIONAHEALTHY, where k=2.25 ± 0.15. Airway resistances in the simulated SGS models were similar to resistances in models based on CT scans of actual SGS patients, suggesting that our simulated SGS models were representative of airway resistance in actual SGS patients. CONCLUSION:Our computer simulations suggest that the degree of airflow limitation in SGS patients may be estimated based on anatomic measurements alone. Future studies are recommended to test these predictions in larger cohorts. LEVEL OF EVIDENCE:4. Laryngoscope, 128:1551-1557, 2018.

Project description:UnlabelledLung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD) progresses, but their role in pathogenesis remains controversial. To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant. Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis. In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a) stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b) the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production. Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines. This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length. As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts. Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry); by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent). Aberrant lung CD4+ T cells polarization appears to be common in advanced COPD, but also exists in some smokers with normal spirometry, and may contribute to development and progression of specific COPD phenotypes.Trial registrationClinicalTrials.gov as NCT00281229.

Dataset Information

Mechanisms affecting exercise ventilatory inefficiency-airflow obstruction relationship in male patients with chronic obstructive pulmonary disease.

Background

Methods

Results

Conclusion

Trial registration

Publications

Mechanisms affecting exercise ventilatory inefficiency-airflow obstruction relationship in male patients with chronic obstructive pulmonary disease.

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