An Impairment in Resting and Exertional Breathing Pattern May Occur in Long-COVID Patients with Normal Spirometry and Unexplained Dyspnoea.

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (TI) during the tidal volume (VT) to the total breath duration (TI/TTOT) and by the VT/TI ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed TI/TTOT and VT/TI at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O2 uptake (VO2peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of TI/TTOT at rest and at peak, and lower values in VT/TI at peak (p < 0.05). In LC patients, values of TI/TTOT at peak were significantly related to ∆PETCO2, i.e., the end-tidal pressure of CO2 at peak minus the one at rest (p < 0.05). When LC patients were categorized by the TI/TTOT 0.38 cut-off value, patients with TI/TTOT > 0.38 showed lower values in VO2peak and maximal workload, and greater values in the ventilation/CO2 linear relationship slope than patients with TI/TTOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

Reduced exercise ventilatory efficiency in adults with cystic fibrosis and normal to moderately impaired lung function.

Despite being a hallmark and an independent prognostic factor in several cardiopulmonary diseases, ventilatory efficiency-i.e., minute ventilation/carbon dioxide output relationship (V̇e/V̇co2)-has never been systematically explored in cystic fibrosis (CF). To provide a comprehensive frame of reference regarding measures of ventilatory efficiency in CF adults with normal to moderately impaired lung function and to confirm the hypothesis that V̇e/V̇co2 is a sensitive marker of early lung disease. CF patients were divided into three groups, according to their spirometry: normal (G1), mild impairment (G2), and moderate impairment (G3) in lung function. All participants underwent incremental cardiopulmonary exercise testing on a cycle ergometer. Lowest V̇e/V̇co2 ratio (nadir) and the slope and the intercept of the linear region of the V̇e/V̇co2 relationship were contrasted in a two-center retrospective analysis, involving 72 CF patients and 36 healthy controls (HC). Compared with HC, CF patients had significantly higher V̇e/V̇co2 nadir, slope, and intercept (P < 0.001, P < 0.001, and P = 0.049, respectively). Subgroup analysis revealed significant differences in nadir (P = 0.001) and slope (P = 0.012) values even between HC and G1. Dynamic hyperinflation related negatively with slope (P = 0.045) and positively with intercept (P = 0.001), while no impact on nadir was observed. Ventilatory inefficiency is a clear feature of adults with CF, even among patients with normal spirometry. V̇e/V̇co2 nadir seems to be the most reliable metric to describe ventilatory efficiency in CF adults. Further prospective studies are needed to clarify whether V̇e/V̇co2 could represent a useful marker in the evaluation of early lung disease in CF.NEW & NOTEWORTHY This is the first study to investigate ventilatory efficiency in a cohort of adult cystic fibrosis (CF) patients with nonsevere lung disease. The finding of impaired ventilatory efficiency in patients with normal lung function confirms the higher sensitivity of exercise testing in detecting early lung disease compared with spirometry. Dynamic hyperinflation plays a significant role in determining the behavior of V̇e/V̇co2 slope and intercept values with increasing lung function impairment. Apparently free from interference from mechanical constraints, V̇e/V̇co2 nadir seems the most reliable parameter to evaluate ventilatory efficiency in CF adults.

The value of high-resolution computed tomography (HRCT) to determine exercise ventilatory inefficiency and dynamic hyperinflation in adult patients with cystic fibrosis.

INTRODUCTION: In Cystic Fibrosis (CF), exercise ventilatory inefficiency and dynamic hyperinflation (DH) cause exercise limitation and induce poor exercise tolerance. High-resolution computed tomography (HRCT) of the lung can detect pulmonary abnormalities in CF patients. We aimed to identify the determinants of exercise ventilatory inefficiency and DH using HRCT-derived metrics. METHODS: Fifty-two adult CF patients were prospectively enrolled; all participants underwent cardio-pulmonary exercise test (CPET) and HRCT. Radiological impairment was evaluated by the Brody II scoring system. Slope and intercept of the minute ventilation/CO2 production (V'E/V'CO2) regression line and the ratio of inspiratory capacity/total lung capacity (IC/TLC) at rest and at peak of exercise were measured. RESULTS: Four groups of patients were identified based on the combination of ventilatory efficiency (Vef) or inefficiency (Vin) and the presence/absence of DH. Compared to other groups, CF adults with Vin and DH had worse functional status and higher total (T), bronchiectasis (B) and air trapping (AT) scores at HRCT. Significant correlations were found between V'E/V'CO2 intercept and V'E/V'CO2 slope (ρ - 0.455, p = 0.001) and between V'E/V'CO2 intercept and Δ inspiratory capacity (IC) (ρ - 0.334, p = 0.015). Regression analysis identified AT score (cut-off 7.9, odds ratio-OR 3.50) as the only independent predictor of Vin and T (cut-off 53.6, OR 4.98), B (cut-off 16.1, OR 4.88), airways wall thickening (AWT) (cut-off 13, OR 3.41), and mucous plugging (MP) scores (cut-off 11.7, OR 4.18) as significant predictors of DH. CONCLUSION: In adult CF cohort, values of HRCT metrics are determinants of Vin (AT) and DH (T, B, AWT, MP).

A High Degree of Dyspnea Is Associated With Poor Maximum Exercise Capacity in Subjects With COPD With the Same Severity of Air-Flow Obstruction.

BACKGROUND: In patients with COPD, limited data have been reported concerning the association between dyspnea perception and exercise tests. Moreover, the perception of dyspnea has not been analyzed in patients with the same severity of air-flow obstruction. The aim of our study was to evaluate the relationship between the degree of dyspnea and exercise capacity in subjects with COPD who had the same severity of air-flow obstruction. METHODS: We assessed dyspnea perception and maximum exercise capacity by using the modified Medical Research Council dyspnea scale (mMRC) questionnaire and by using the symptom-limited incremental cardiopulmonary exercise test, respectively. A propensity score matching was used to obtain the balance between the subjects with COPD and with an mMRC questionnaire score <2 and ≥2 (mMRC score) according to the severity of air-flow obstruction. RESULTS: A total of 249 ambulatory adult patients with stable COPD (mean age, 68 y) were considered in the full cohort. After propensity score analysis, 160 subjects (65% men; mean ± SD FEV1, 47.5 ± 12.8% of predicted) were included in our study cohort. The subjects with an mMRC questionnaire score ≥2 in comparison with those with an mMRC questionnaire score <2 showed lower values in oxygen uptake at peak (VO2 max) (P = .002) and in maximum work load (P < .001). In the regression models, the mMRC questionnaire score was able to predict oxygen uptake at peak (P < .001) and at maximum work load (P < .001). CONCLUSIONS: In subjects with COPD and with the same severity of air-flow obstruction, a high score in dyspnea was related to a poor maximum exercise capacity. Our results support the view that, in COPD, the severity of air-flow obstruction was less informative than symptoms in the combined assessment of the disease.

Heart rate recovery is associated with ventilatory constraints and excess ventilation during exercise in patients with chronic obstructive pulmonary disease.

Background Heart rate recovery delay is a marker of cardiac autonomic dysfunction. In chronic obstructive pulmonary disease patients, the ventilatory response to exercise during incremental cardiopulmonary exercise test may add information about dynamic hyperinflation by low values of inspiratory capacity/total lung capacity ratio (at peak) and excess ventilation by the slope of minute ventilation to carbon dioxide output ratio (VE/VCO2 slope). We aimed to assess if the ventilatory response to exercise might be a determinant for heart rate recovery delay. Design An observational, prospective study. Methods Anthropometric characteristics, lung function and cardiopulmonary exercise test data were recorded in chronic obstructive pulmonary disease outpatients. A cut-off of heart rate recovery of 12 or more beats was used to define heart rate recovery delay. Results Of 254 patients enrolled, 156 (61%) showed heart rate recovery delay. As compared to patients with normal heart rate recovery, patients with delay were older, with a worse lung function and with lower values of peak oxygen uptake, maximal workload, oxygen pulse at rest and at peak, and inspiratory capacity/total lung capacity at peak. Conversely, VE/VCO2 slope and dyspnoea and leg fatigue perception at peak were higher in patients with heart rate recovery delay. In the multivariate regression model adjusted for age, sex, fat-free mass, heart rate at rest and use of ß-blockers, we found that inspiratory capacity/total lung capacity at peak (<0.25) (odds ratio 2.61; P = 0.007) and VE/VCO2 slope (>32) (odds ratio 2.26; P = 0.018) predict the risk of heart rate recovery delay. Conclusions In chronic obstructive pulmonary disease outpatients, heart rate recovery is associated with dynamic hyperinflation and excess ventilation during exercise.

Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation.

Background Silent/asymptomatic peripheral artery disease may occur in patients with chronic obstructive pulmonary disease, but it is poorly investigated. The primary aim of this study was to evaluate in chronic obstructive pulmonary disease patients the impact of asymptomatic/silent peripheral artery disease on maximal exercise capacity; the secondary aim was to search for predictors of peripheral artery disease. Methods We prospectively enrolled chronic obstructive pulmonary disease outpatients. Data on anthropometric characteristics, lung function, cardiopulmonary exercise test and ankle-brachial index were recorded. The cut-off of ankle-brachial index used to define patients with peripheral artery disease was ≤0.90. Results We studied 47 patients and found 24 patients (51%) who showed peripheral artery disease. As compared to patients without peripheral artery disease, patients with peripheral artery disease had lower values of peak oxygen uptake, peak workload, energy expenditure (metabolic equivalents) and heart rate recovery, but showed the same degree of airflow obstruction and static and dynamic hyperinflation. In a multivariate linear regression model performed to identify variables predicting metabolic equivalents, ankle-brachial index (ß 2.59; 95% confidence interval 0.51-4.67; p = 0.016) was an independent variable. In the search for predictors of peripheral artery disease, heart rate recovery (odds ratio 8.80; 95% confidence interval 1.30-59.35; p = 0.026) increased the risk of peripheral artery disease, whereas metabolic equivalents (odds ratio 0.50; 95% confidence interval 0.26-0.94, p = 0.033) and inhaled corticosteroids+long-acting ß2 agonists (odds ratio 0.13; 95% confidence interval 0.02-0.83; p = 0.030) reduced this risk. Conclusions In chronic obstructive pulmonary disease outpatients, asymptomatic/silent peripheral artery disease affects the maximal exercise capacity regardless of airflow obstruction and lung hyperinflation. A delay of heart rate recovery increase the risk of peripheral artery disease, whereas high values of metabolic equivalents and the use of inhaled corticosteroids+long-acting ß2 agonists reduces this risk.

Prevalence of Small-Airway Dysfunction among COPD Patients with Different GOLD Stages and Its Role in the Impact of Disease.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) patients, small-airway dysfunction (SAD) is considered a functional hallmark of disease. However, the exact role of SAD in the clinical presentation of COPD is not yet completely understood; moreover, it is not known whether SAD may have a relationship with the impact of disease. OBJECTIVES: To evaluate the prevalence of SAD among COPD patients categorized by the old and the new GOLD classification and to ascertain whether there is a relationship between SAD and impact of disease measured by the COPD Assessment Test (CAT) questionnaire. METHODS: We prospectively enrolled COPD outpatients from the University Hospital of Parma. Using the impulse oscillometry system (IOS), we assessed the fall in resistance from 5 to 20 Hz (R5-R20), reactance at 5 Hz (X5), and resonant frequency (FRes) as markers of peripheral airway dysfunction. According to R5-R20 ≥0.07 or <0.07, the cohort was also categorized in patients with and without SAD, respectively. RESULTS: We studied 202 patients. In both GOLD classifications, a progressive increasing distribution of R5-R20 and FRes was reported with a decreasing of X5. Moreover, there was a significant correlation between R5-R20 and CAT (r = 0.527, p < 0.001). Finally, the presence of SAD (OR 11.96; 95% CI 4.53-31.58; p < 0.001) and use of ICS + LABA + LAMA (OR 5.31; 95% CI 1.88-15.02; p = 0.002) were independent predictors of higher impact (CAT score ≥10). CONCLUSION: In COPD patients, the presence of SAD, as assessed by IOS, progressively increases with GOLD classifications and it is closely related to the high impact of disease on health status.

Relationships between emphysema and airways metrics at High-Resolution Computed Tomography (HRCT) and ventilatory response to exercise in mild to moderate COPD patients.

BACKGROUND AND PURPOSE: In Chronic Obstructive Pulmonary Disease (COPD) patients, the opportunity to carry out a thoracic high-resolution CT (HRCT) scan and to perform an incremental cardiopulmonary exercise test (CPET) increases the possibility to identify the different clinical features of disease. The aim of our study was to evaluate the relationships between HRCT metrics (on emphysema by low attenuation areas-LAA% and airways by wall area-WA%) and CPET variables related to the dynamic response to exercise in terms of elastic balance (Δ rest-to-peak IC/TLC) and ventilation capacity for carbon dioxide output (VE/VCO2slope and VE/VCO2 intercept). METHODS: We prospectively enrolled COPD outpatients from the University Hospital of Parma. Data on anthropometrics characteristics, lung function, HRCT (LAA% and WA%) and CPET (Δ rest-to-peak IC/TLC, VE/VCO2 slope and VE/VCO2 intercept) were recorded. RESULTS: Fifty-one mild to moderate COPD patients (66% males; median age 70 y; mean FEV1 56% of pred.) were enrolled in the study. LAA% demonstrated a significant correlation with Δ rest-to-peak IC/TLC and VE/VCO2slope (r = 0.405, p = 0.005 and r = 0.453, p = 0.001, respectively), while WA% with VE/VCO2slope (r = -0.333, p = 0.020). In multivariate regression models, after adjustment for oxygen uptake (peak VO2) and physical capacity (peak workload), LAA was the only independent predictor of Δ rest-to-peak IC/TLC (ß 0.774, SE 0.334, p = 0.025) and VE/VCO2 slope (ß 0.155, SE 0.053, p = 0.005 and ß 0.305, SE 0.123, p = 0.018, respectively). VE/VCO2 intercept was instead predicted from FEV1 only (ß -0.097, SE 0.042, p = 0.027). CONCLUSION: In mild to moderate COPD patients, emphysema (LAA) and airways metrics (WA) have close relationships with the different characteristics of ventilatory response to exercise. In particular, we were able to show that LAA is an independent predictor of exercise-induced Δ rest-to-peak IC/TLC and VE/VCO2 slope.

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

BACKGROUND: We investigated whether a relationship between small airways dysfunction and bronchodilator responsiveness exists in patients with chronic obstructive pulmonary disease (COPD). METHODS: We 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). RESULTS: Eighty 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. CONCLUSION: This 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.

Small airway dysfunction is associated to excessive bronchoconstriction in asthmatic patients.

BACKGROUND: We investigated whether a relationship between small airways dysfunction and bronchial hyperresponsiveness (BHR), expressed both in terms of ease of airway narrowing and of excessive bronchoconstriction, could be demonstrated in asthma. METHODS: 63 (36 F; mean age 42 yr ± 14) stable, mild-to-moderate asthmatic patients (FEV1 92% pred ±14; FEV1/FVC 75% ± 8) underwent the methacholine challenge test (MCT). The degree of BHR was expressed as PD20 (in µg) and as ∆FVC%. Peripheral airway resistance was measured pre- and post-MCT by impulse oscillometry system (IOS) and expressed as R5-R20 (in kPa sL-1). RESULTS: All patients showed BHR to methacholine (PD20 < 1600 µg) with a PD20 geometric (95% CI) mean value of 181(132-249) µg and a ∆FVC% mean value of 13.6% ± 5.1, ranging 2.5 to 29.5%. 30 out of 63 patients had R5-R20 > 0.03 kPa sL-1 (>upper normal limit) and showed ∆FVC%, but not PD20 values significantly different from the 33 patients who had R5-R20 ≤ 0.03 kPa sL-1 (15.8% ± 4.6 vs 11.5% ± 4.8, p < 0.01 and 156(96-254) µg vs 207 (134-322) µg, p = 0.382). In addition, ∆FVC% values were significantly related to the corresponding pre- (r = 0.451, p < 0.001) and post-MCT (r = 0.376, p < 0.01) R5-R20 values. CONCLUSIONS: Our results show that in asthmatic patients, small airway dysfunction, as assessed by IOS, is strictly associated to BHR, expressed as excessive bronchoconstriction, but not as ease of airway narrowing.

Maximal exercise in obese patients with COPD: the role of fat free mass.

BACKGROUND: Obese patients (OB) with COPD may better tolerate exercise as compared to normal weight (NW) COPD patients, even if the reason for this is not yet fully understood. We investigated the interactions between obesity, lung hyperinflation, fat-free mass (FFM) and exercise capacity in COPD. METHODS: Forty-four patients (16 females; age 65 ± 8 yrs) were assessed by resting lung function and body composition and exercised on a cycle-ergometer to exhaustion. RESULTS: Twenty-two OB and 22 NW patients did not differ in age, gender and airflow obstruction degree, but in FFM (p < 0.05). OB had significantly higher values in inspiratory capacity/total lung capacity ratio (IC/TLC) at rest (p < 0.01), but not at peak of exercise and showed significantly higher values in peak workload (p < 0.05) and in peak oxygen uptake (VO2), when expressed as absolute value (p < 0.05), but not when corrected by FFM. OB compared to NW experienced lower leg fatigue (p < 0.05), but similar dyspnea on exertion. In all patients, the regression equation by stepwise multiple regression analysis for peak workload and VO2, as dependent variables included both FFM and IC/TLC at rest, as independent variables (r(2) = 0.43 and 0.37, respectively). CONCLUSIONS: OB with COPD, as compared to NW patients matched for age, gender and airflow obstruction, had greater FFM and less resting lung hyperinflation and showed greater maximal exercise capacity. Pulmonary and non-pulmonary factors may explain the preservation of exercise tolerance in patients with COPD associated with obesity.

Excess ventilation and ventilatory constraints during exercise in patients with chronic obstructive pulmonary disease.

We assessed the relationship between minute ventilation/carbon dioxide output (VE/VCO2) and ventilatory constraints during an incremental cardiopulmonary exercise testing (CPET) in patients with chronic obstructive pulmonary disease (COPD). Slope and intercept of the VE/VCO2 linear relationship, the ratios of inspiratory capacity/total lung capacity (IC/TLC) and of tidal volume (VT) over vital capacity (VTpeak/VC) and IC (VTpeak/IC) and over forced expiratory volume at 1st second (VTpeak/FEV1) at peak of exercise were measured in 52 COPD patients during a CPET. The difference peak-rest in end-tidal pressure of CO2 (PETCO2) was also measured. VE/VCO2 intercept showed a negative correlation with IC/TLC peak (p<0.01) and a positive one with VTpeak/FEV1 (p<0.01) and with PETCO2 peak-rest (p<0.01). VE/VCO2 slope was negatively related to VTpeak/VC, VTpeak/IC and VTpeak/FEV1 (all correlations p<0.05) and to PETCO2 peak-rest (p<0.01). In COPD, VE/VCO2 slope and intercept provide complementary information on the ventilatory limitation to exercise, as assessed by changes in the end-expiratory lung volume and in tidal volume excursion.

Ventilatory response to carbon dioxide output in subjects with congestive heart failure and in patients with COPD with comparable exercise capacity.

BACKGROUND: Patients with congestive heart failure or COPD may share an increased response in minute ventilation (V̇E) to carbon dioxide output (V̇CO2 ) during exercise. The goal of this study was to ascertain whether the V̇E/V̇CO2 slope and V̇E/V̇CO2 intercept can discriminate between subjects with congestive heart failure and those with COPD at equal peak oxygen uptake (V̇O2 ). METHODS: We studied 46 subjects with congestive heart failure (mean age 61 ± 9 y) and 46 subjects with COPD (mean age 64 ± 8 y) who performed a cardiopulmonary exercise test. RESULTS: The V̇E/V̇CO2 slope was significantly higher in subjects with congestive heart failure compared with those with COPD (39.5 ± 9.5 vs 31.8 ± 7.4, P < .01) at peak V̇O2 < 16 mL/kg/min, but not ≥ 16 mL/kg/min (28.3 ± 5.3 vs 28.9 ± 6.6). The V̇E/V̇CO2 intercept was significantly higher in both subgroups of subjects with COPD compared with the corresponding values in the subjects with congestive heart failure (3.60 ± 1.7 vs -0.16 ± 1.7 L/min, P < .01; 3.63 ± 2.7 vs 0.87 ± 1.5 L/min, P < .01). According to receiver operating characteristic curve analysis, when all subjects with peak V̇O2 < 16 mL/kg/min were considered, subjects with COPD had a higher likelihood to have the V̇E/V̇CO2 intercept > 2.14 L/min (0.92 sensitivity, 0.96 specificity). Regardless of peak V̇O2 , the end-tidal pressure of CO2 (PETCO2 ) at peak exercise was not different in subjects with congestive heart failure (P = .42) and was significantly higher in subjects with COPD (P < .01) compared with the corresponding unloaded PETCO2 . CONCLUSIONS: The ventilatory response to V̇CO2 during exercise was significantly different between subjects with congestive heart failure and those with COPD in terms of the V̇E/V̇CO2 slope with moderate-to-severe reduction in exercise capacity and in terms of the V̇E/V̇CO2 intercept regardless of exercise capacity.

Fat-free mass depletion is associated with poor exercise capacity irrespective of dynamic hyperinflation in COPD patients.

BACKGROUND: In patients with COPD, we investigated the effect of the fat-free mass (FFM) on maximal exercise capacity and the relationship with changes in operational lung volumes during exercise. METHODS: In a cross-sectional study 57 patients (16 females; age 65 ± 8 y) were consecutively assessed by resting lung function, symptom-limited cardiopulmonary exercise test, and body composition by means of bioelectrical impedance analysis to measure the FFM index (FFMI; in kilograms per square meter). RESULTS: Patients were categorized as depleted (n = 14) or nondepleted (n = 43) according to FFMI. No significant difference in gender, age, and resting lung function was found between depleted and nondepleted patients. When compared with nondepleted COPD patients, the depleted COPD patients had a significantly lower O2 uptake at the peak of exercise and at anaerobic threshold as well as at peak oxygen pulse, oxygen uptake efficiency slope (OUES), and heart rate recovery (HRR) (P < .05 for all comparisons), but similar inspiratory capacity/total lung capacity at the peak of exercise. Moreover, they also reported significantly higher leg fatigue (P < .05), but not dyspnea on exertion. In all patients, significant correlations (P < .01) were found between FFMI and peak oxygen pulse, OUES, HRR, and leg fatigue. CONCLUSIONS: This study shows that FFM depletion plays a part in the reduction of exercise capacity in COPD patients, regardless of dynamic hyperinflation, and is strictly associated with poor cardiovascular response to exercise and to leg fatigue, but not with dyspnea.

Pulmonary rehabilitation improves cardiovascular response to exercise in COPD.

BACKGROUND: Pulmonary rehabilitation (PR) has emerged as a recommended standard of care in symptomatic COPD. OBJECTIVES: We now studied whether PR may affect cardiovascular response to exercise in these patients. METHODS: Twenty-seven patients (9 females aged 69 ± 8 years) with moderate-to-severe airflow obstruction admitted to a 9-week PR course performed a pre-to-post evaluation of lung function test and symptom-limited cardiopulmonary exercise test (CPET). Oxygen uptake (VO2), tidal volume (V(T)), dyspnea and leg fatigue scores were measured during CPET. Cardiovas-cular response was assessed by means of oxygen pulse (O2Pulse), the oxygen uptake efficiency slope and heart rate recovery at the 1st min. RESULTS: A significant increase in peak VO2 and in all cardiovascular parameters (p < 0.05) was found following PR when compared to baseline. Leg fatigue (p < 0.05), but not dyspnea, was significantly reduced after PR. When assessed at metabolic and ventilatory iso levels [% VCO2max and % minute ventilation (VEmax)], O2Pulse and V(T) were significantly higher (p < 0.05) at submaximal exercise (75 and 50% of VCO2max and VEmax) after PR when compared to baseline. V(T) percent changes at 75% VCO2max and 75% VEmax after PR significantly correlated with corresponding changes in O2Pulse (p < 0.01). CONCLUSIONS: In COPD patients, a PR training program improved the cardiovascular response during exercise at submaximal exercise independent of the external workload. This change was associated with an enhanced ventilatory function during exercise.

Small airway dysfunction by impulse oscillometry in asthmatic patients with normal forced expiratory volume in the 1st second values.

Small airways are relevant to the pathophysiology of asthma. We investigated whether in asthmatic patients with normal forced expiratory volume in the 1st second (FEV(1)) values, impulse oscillometry system (IOS), as a measure of small airway function, contributed additional information to spirometry either at baseline or after bronchodilator, and whether it was related to the disease control. The fall in resistance from 5 to 20 Hz (R5-R20) and reactance at 5 Hz (X5) by IOS and spirometry measures of small airway function (forced expiratory flow at 25-75% [FEF(25-75)] and forced vital capacity/slow inspiratory vital capacity [FVC/SVC]) at baseline and after 400 micrograms of salbutamol were prospectively measured in 33 asthmatic patients (18 women; age range, 18-66 years). Disease control was assessed by the Asthma Control Test (ACT). R5-R20 but not X5 values were significantly related to FEF(25-75) and FVC/SVC values (p < 0.05 for both correlations). When the bronchodilator response was assessed, no correlation was found among IOS and spirometry changes. ACT scores were related to R5-R20, FEF(25-75), and FVC/SVC values (p < 0.01 for all correlations). In asthmatic patients with normal FEV(1) values, R5-R20 values were related to spirometry measures of small airway function. However, when the bronchodilator response was assessed, IOS and spirometry provided quite different results. Moreover, small airway dysfunction, as assessed by IOS and spirometry, was associated with poor disease control and history of asthma exacerbations. The results of this study confirm the value of IOS, as an investigative tool, and suggest that in asthmatic patients with normal FEV(1) values and poor disease control, small airway function should be investigated.

Overweight is associated with airflow obstruction and poor disease control but not with exhaled nitric oxide change in an asthmatic population.

BACKGROUND: The role of an elevated body mass index (BMI) in asthma remains controversial. OBJECTIVES: To investigate the relationship between overweight (BMI >25 and ≤30), lung function, disease control, and airway inflammation in an asthmatic population. METHODS: We consecutively studied 348 patients (age 43 ± 16 years; 211 females). In all patients, BMI, spirometry, the Asthma Control Test (ACT), and fractional exhaled nitric oxide (FeNO; ppb) were measured. RESULTS: One hundred forty-five patients were overweight and, as compared to those with normal BMI, had lower values of FVC, FEV(1), and FEV(1)/FVC and of FEF(25-75) even when normalized for FVC (p < 0.05 for each comparison). The ratio between the number of patients with well-controlled asthma (ACT ≥20) and that of patients with poorly controlled asthma (ACT < 20) was significantly lower in overweight patients (1.07 vs. 1.84; χ(2) = 6.030, p < 0.01). In overweight patients, the odds ratio of uncontrolled asthma expressed by logistic regression analysis was 1.632 (95% CI = 1.043-2.553), independently of gender, atopy, smoking habit, and inhaled steroid therapy. No difference was observed in FeNO values between overweight and normal weight patients (27.7 ± 2.3 vs. 27.9 ± 2.2 ppb). CONCLUSIONS: Our results show that, in an asthmatic population, overweight is associated with airflow obstruction and poor disease control but not with FeNO change. The findings of the present study support the view that other factors besides airway inflammation alone may explain the relationship between asthma and an elevated BMI.

Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients.

BACKGROUND: Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients. METHODS: We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation. RESULTS: Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively. CONCLUSION: The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.

Effects of beclomethasone/formoterol fixed combination on lung hyperinflation and dyspnea in COPD patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by airflow obstruction and lung hyperinflation leading to dyspnea and exercise capacity limitation. OBJECTIVES: The present study was designed to evaluate whether an extra-fine combination of beclomethasone and formoterol (BDP/F) was effective in reducing air trapping in COPD patients with hyperinflation. Fluticasone salmeterol (FP/S) combination treatment was the active control. METHODS: COPD patients with forced expiratory volume in one second <65% and plethysmographic functional residual capacity ≥120% of predicted were randomized to a double-blind, double-dummy, 12-week, parallel group, treatment with either BDP/F 400/24 µg/day or FP/S 500/100 µg/day. Lung volumes were measured with full body plethysmography, and dyspnea was measured with transition dyspnea index. RESULTS: Eighteen patients were evaluable for intention to treat. A significant reduction in air trapping and clinically meaningful improvement in transition dyspnea index total score was detected in the BDP/F group but not in the FP/S group. Functional residual capacity, residual volume (RV) and total lung capacity significantly improved from baseline in the BDP/F group only. With regard to group comparison, a significantly greater reduction in RV was observed with BDP/F versus FP/S. CONCLUSION: BDP/F extra-fine combination is effective in reducing air trapping and dyspnea in COPD patients with lung hyperinflation.

Patient assessment and prevention of pulmonary side-effects in surgery.

PURPOSE: The review deals with the clinical and functional assessment that is requested before surgical operations and with the pulmonary effects of surgery. Moreover, an evidence-based approach to prevent postoperative pulmonary complications is provided. RECENT FINDINGS: Spirometry is recommended for patients with a history of tobacco use or dyspnoea who are considered for cardiac or upper abdominal surgery and for all patients who are candidates for lung resection. For patients undergoing lung resection, low complication rates have been associated with a preoperative forced expiratory volume at first second value of at least 2 litres or 80% of the predicted value and at least 1.5 litres or 60% of the predicted value in the case of pneumonectomy or lobectomy, respectively. At-risk patients are recommended to undergo split lung function studies to estimate the residual parenchyma function after surgery. In patients with borderline estimated values, a cardiopulmonary exercise test is recommended to stratify further risk. Preventive interventions of postoperative pulmonary complications, including pain control, respiratory chest physiotherapy and continuous positive airway pressure may effectively reduce the occurrence of pulmonary complications. SUMMARY: Pulmonary functional assessment is relevant in patients candidates for surgery. The prevention of the postoperative pulmonary complications is one of the most important goals of the treatment of patients undergoing surgery.