Dynamic hyperinflation is a risk factor for mortality and severe exacerbations in COPD patients.

OBJECTIVE: To assess if dynamic hyperinflation is an independent risk factor for mortality and severe exacerbations in COPD patients. METHODS: A cohort of 141 patients with stable COPD and moderate to very severe airflow limitation, treated according to conventional guidelines, was followed for a median of 9 years. Clinical characteristics were recorded and arterial blood gases, pulmonary function tests, 6-min walk and incremental exercise test with measurement of respiratory pattern and operative lung volumes were performed. Endpoints were all-cause mortality and hospitalization for COPD exacerbation. RESULTS: 58 patients died during the follow-up period (1228 patients x year). The mortality rate was higher in patients with dynamic hyperinflation (n = 106) than in those without it (n = 35) (14.6; 95% CI, 14.5-14.8 vs. 7.2; 95% CI, 7.1-7.4 per 1000 patients-year). After adjusting for sex, age, body mass index, pack-years and treatment with inhaled corticosteroids, dynamic hyperinflation was associated with a higher mortality risk (adjusted hazard ratio [aHR], 2.725; 95% CI, 1.010-8.161), and in a multivariate model, comorbidity, peak oxygen uptake and dynamic hyperinflation were retained as independent predictors of mortality. The time until first severe exacerbation was shorter for patients with dynamic hyperinflation (aHR, 3.961; 95% CI, 1.385-11.328), and dynamic hyperinflation, FEV1 and diffusing capacity were retained as independent risk factors for severe exacerbation. Moreover, patients with dynamic hyperinflation had a higher hospitalization risk than those without it (adjusted incidence rate ratio, 1.574; 95% CI, 1.087-2.581). CONCLUSION: In stable COPD patients, dynamic hyperinflation is an independent prognostic factor for mortality and severe exacerbations.

Critical Care Management of Severe Asthma Exacerbations.

Severe asthma exacerbations, including near-fatal asthma (NFA), have high morbidity and mortality. Mechanical ventilation of patients with severe asthma is difficult due to the complex pathophysiology resulting from severe bronchospasm and dynamic hyperinflation. Life-threatening complications of traditional ventilation strategies in asthma exacerbations include the development of systemic hypotension from hyperinflation, air trapping, and pneumothoraces. Optimizing pharmacologic techniques and ventilation strategies is crucial to treat the underlying bronchospasm. Despite optimal pharmacologic management and mechanical ventilation, the mortality rate of patients with severe asthma in intensive care units is 8%, suggesting a need for advanced non-pharmacologic therapies, including extracorporeal life support (ECLS). This review focuses on the pathophysiology of acute asthma exacerbations, ventilation management including non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV), the pharmacologic management of acute asthma, and ECLS. This review also explores additional advanced non-pharmacologic techniques and monitoring tools for the safe and effective management of critically ill adult asthmatic patients.

Effect of a Conical-PEP Mask on Exercise in Subjects With COPD.

BACKGROUND: Dynamic hyperinflation (DH) is a major pathophysiology of COPD that is directly related to dyspnea and exercise intolerance. Positive expiratory pressure (PEP) might reduce DH and dyspnea during exercise, but at present, there is insufficient evidence to conclude whether it is beneficial for DH, dyspnea, and exercise capacity in COPD. METHODS: A randomized crossover trial with concealed allocation was conducted in 37 moderate to very severe subjects with COPD (34 males, age 66.6 ± 7.4 y, FEV1% of predicted 56.3 ± 13.7). The experimental condition was conical-PEP breathing with a PEP of around 5 cm H2O during a spot marching exercise at a constant speed, inducing 71 ± 9% age-predicted maximum heart rate to symptom limit or 25 min. The control condition was usual breathing. Exercise endurance time and end-exercise symptoms were recorded. Inspiratory capacity (IC) was measured pre-exercise and immediately post exercise. Cardiopulmonary function and breathlessness were monitored throughout the test and after 10 min of recovery. RESULTS: There were no complications or adverse effects during exercise with a conical-PEP mask. Conical-PEP showed longer exercise times than control (median 11.0 [interquartile range 7.7-17.0] min vs 8 [6.0-11.5] min, respectively, P < .001). Most stopped exercising because of breathlessness and leg fatigue. At the end of exercise, IC and breathlessness showed non-significant differences between the conditions, but breathlessness was significantly lower in conical-PEP (median 4 [1.5-5.0] than control 5 [3-6] on Borg scale at isotime for control [8 min]). CONCLUSIONS: Breathing with a 5 cm H2O conical-PEP mask improved exercise time (median 27.1% [0.6-52.9]) in subjects with COPD. The improvement in exercise with the conical-PEP mask was associated with slower development of breathlessness, possibly due to delays in DH development.

Dynamic Hyperinflation While Exercising-A Potential Predictor of Pulmonary Deterioration in Cystic Fibrosis.

BACKGROUND: Lung function deterioration in cystic fibrosis (CF) is typically measured by a decline in the forced expiratory volume in one second (FEV1%), which is thought to be a late marker of lung disease. Dynamic hyperinflation (DH) is seen in obstructive lung diseases while exercising. Our aim was to assess whether DH could predict pulmonary deterioration in CF; a secondary measure was the peak VO2. METHODS: A retrospective study was conducted of people with CF who performed cardiopulmonary exercise tests (CPETs) during 2012-2018. The tests were classified as those demonstrating DH non-DH. Demographic, genetic, and clinical data until 12.2022 were extracted from patient charts. RESULTS: A total of 33 patients aged 10-61 years performed 41 valid CPETs with valid DH measurements; sixteen (39%) demonstrated DH. At the time of the CPETs, there was no difference in the FEV1% measurements between the DH and non-DH groups (median 83.5% vs. 87.6%, respectively; p = 0.174). The FEV1% trend over 4 years showed a decline in the DH group compared to the non-DH group (p = 0.009). A correlation was found between DH and the lung clearance index (LCI), as well as the FEV1% (r = 0.36 and p = 0.019 and r = -0.55 and p = 0.004, respectively). Intravenous (IV) antibiotic courses during the 4 years after the CPETs were significantly more frequent in the DH group (p = 0.046). The peak VO2 also correlated with the FEV1% and LCI (r = 0.36 and p = 0.02 and r = -0.46 and p = 0.014, respectively) as well as with the IV antibiotic courses (r = -0.46 and p = 0.014). CONCLUSIONS: In our cohort, the DH and peak VO2 were both associated with lung function deterioration and more frequent pulmonary exacerbations. DH may serve as a marker to predict pulmonary deterioration in people with CF.

Impact of bronchoscopic lung volume reduction with endobronchial valves on dynamic hyperinflation: Results from the PIERCE study.

BACKGROUND AND OBJECTIVE: Dynamic hyperinflation (DH) is a major marker of exertional dyspnoea in severe emphysema. We hypothesized that bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBVs) decreases DH. METHODS: In this prospective bi-centre study from both Toulouse and Limoges Hospitals, we assessed DH during an incremental cycle ergometry before and 3 months after EBVs treatment. The primary objective was to observe the change in inspiratory capacity (IC) at isotime. Target lobe volume reduction (TLVR) and changes in residual volume (RV), forced expiratory volume in one-second (FEV1 ), mMRC, 6 minutes walking distance (6MWD), BODE and other dynamic measures like tele-expiratory volume (EELV) were also analysed. RESULTS: Thirty-nine patients were included, of whom thirty-eight presented DH. IC and EELV at isotime significantly improved (+214 mL, p = 0.004; -713 mL, p Ë‚ 0.001, respectively). Mean changes were +177 mL for FEV1 (+19%, p < 0.001), -600 mL for RV (p < 0.0001), +33 m for 6MWD (p < 0.0001), respectively. Patients who responded on RV (>430 mL decrease) and FEV1 (>12% gain) had better improvements compared to non-responders (+368 mL vs. +2 mL; +398 mL vs. -40 mL IC isotime, respectively). On the opposite, in patients who responded on DH (>200 mL IC isotime increase), changes in TLV (-1216 mL vs. -576 mL), FEV1 (+261 mL vs. +101 mL), FVC (+496 mL vs. +128 mL) and RV (-805 mL vs. -418 mL) were greater compared to non-responders. CONCLUSIONS: DH decreases after EBVs treatment, and this improvement is correlated with static changes.

Tidal volume expandability affected by flow, dynamic hyperinflation, and quasi-fixed inspiratory time in patients with COPD and healthy individuals.

Exertional dyspnea (ED) and impaired exercise performance (EP) are mainly caused by dynamic hyperinflation (DH) in chronic obstructive pulmonary disease (COPD) patients by constraining tidal volume expansion at peak exercise (VTpeak). As VTpeak is the product of inspiratory time (TIpeak) and flow (VT/TIpeak), it was hypothesized that VTpeak and VTpeak/total lung capacity (VTpeak/TLC) may be affected by TIpeak and VT/TIpeak. Hence, the study investigated the (1) effect of TIpeak and VT/TIpeak on VTpeak expansion, (2) factors associated with TIpeak, expiratory time (TEpeak), VT/TIpeak, and VTpeak/TLC, and (3) relationships between VT/TIpeak and VTpeak/TLC with ED and EP in COPD patients and controls. The study enrolled 126 male stable COPD patients and 33 sex-matched controls. At peak exercise, TIpeak was similar in all subjects (COPD versus controls, mean ± SD: 0.78 ± 0.17 s versus 0.81 ± 0.20 s, p = NS), whereas the COPD group had lower VT/TIpeak (1.71 ± 0.49 L/s versus 2.58 ± 0.69 L/s, p < .0001) and thus the COPD group had smaller VTpeak (1.31 ± 0.34 L versus 2.01 ± 0.45 L,p < .0001) and VTpeak/TLC (0.22 ± 0.06 vs 0.33 ± 0.05, p < .0001). TIpeak, TEpeak, and VT/TIpeak were mainly affected by exercise effort, whereas VTpeak/TLC was not. TEpeak, VT/TIpeak, and VTpeak/TLC were inversely changed by impaired lung function. TIpeak was not affected by lung function. Dynamic hyperinflation did not occur in the controls, however, VTpeak/TLC was strongly inversely related to DH (r = -0.79) and moderately to strongly related to lung function, ED, and EP in the COPD group. There was a slightly stronger correlation between VTpeak/TLC with ED and EP than VT/TIpeak in the COPD group (|r| = 0.55-0.56 vs 0.38-0.43). In summary, TIpeak was similar in both groups and the key to understanding how flow affects lung expansion. However, the DH volume effect was more important than the flow effect on ED and EP in the COPD group.

Electrical Impedance Tomography Can Be Used to Quantify Lung Hyperinflation during HFOV: The Pilot Study in Pigs.

Dynamic hyperinflation is reported as a potential risk during high-frequency oscillatory ventilation (HFOV), and its existence has been documented both by physical models and by CT. The aim of this study is to determine the suitability of electrical impendence tomography (EIT) for the measurement of dynamic lung hyperinflation and hypoinflation during HFOV. Eleven healthy pigs were anaesthetized and ventilated using HFOV. The difference between the airway pressure at the airway opening and alveolar space was measured by EIT and esophageal balloons at three mean airway pressures (12, 18 and 24 cm H2O) and two inspiratory to expiratory time ratios (1:1, 1:2). The I:E ratio was the primary parameter associated with differences between airway and alveolar pressures. All animals showed hyperinflation at a 1:1 ratio (median 1.9 cm H2O) and hypoinflation at a 1:2 (median -4.0 cm H2O) as measured by EIT. EIT measurements had a linear correlation to esophageal balloon measurements (r2 = -0.915, p = 0.0085). EIT measurements were slightly higher than that of the esophageal balloon transducer with the mean difference of 0.57 cm H2O. Presence of a hyperinflation or hypoinflation was also confirmed independently by chest X-ray. We found that dynamic hyperinflation developed during HFOV may be detected and characterized noninvasively by EIT.

Evidence of ventilatory constraints during exercise in hypermobile Ehlers-Danlos syndrome.

PURPOSE: Hypermobile Ehlers-Danlos syndrome (hEDS) is a connective tissue disorder with many different symptoms such as pain, fatigue, dysautonomia, or respiratory symptoms. Among the respiratory manifestations described, the most frequent are exertional dyspnea and breathing difficulties. Mechanical ventilatory constraints during exercise could participate in these respiratory manifestations. The objective of this study was to explore the response of pulmonary flow-volume loops to exercise in patients with hEDS and to look for dynamic hyperinflation and expiratory flow limitation during exercise. METHODS: For this purpose, breathing pattern and tidal exercise flow-volume loops were recorded at two workloads (30% and 80% of the peak power output) of a constant load exercise test. RESULTS: Twelve patients were included (11 women, mean age 41 ± 14 years). The results showed a decrease (p = 0.028) in the inspiratory capacity (from 3.12 ± 0.49 L to 2.97 ± 0.52 L), an increase (p = 0.025) in the end-expiratory lung volume (from 0.73 ± 0.68 L to 0.88 ± 0.66 L, i.e., from EELV comprising 17 ± 12% to 21 ± 12% of forced vital capacity) between the two workloads in favor of dynamic hyperinflation, and half of the patients had expiratory flow limitations. CONCLUSION: This exploratory study provides evidence for mechanical ventilatory constraints during exercise in patients with hEDS, which may induce discomfort during exercise and could contribute to the respiratory symptomatology. TRIAL REGISTRATION NUMBER: This study is part of a larger clinical trial (ID: NCT04680793, December 2020).

The Six-Minute Stepper Test Is Valid to Evaluate Functional Capacity in Hospitalized Patients With Exacerbated COPD.

Background: The six-minute stepper test (6MST) is a self-paced test considered a valid tool to assess functional capacity in stable COPD patients. However, a high floor effect, where a large proportion of participants reach the minimum score when using the measurement instrument, might compromise the test validity in the hospital setting. Therefore, this study aimed at verifying the concurrent validity of 6MST in hospitalized patients with acute exacerbation of COPD (AECOPD). Methods: A cross-sectional study was conducted in a tertiary hospital. Patients who were hospitalized due to AECOPD were considered for inclusion. On the first day, when patients reached minimum clinical criteria considered as the use of non-invasive ventilation less than 2 h for 6 h/period, dyspnea at rest less than 7 (very severe) on the modified Borg scale, a respiratory rate less than 25 breaths per minute, oxygen pulse saturation greater than 88% (considering use of supplemental oxygen) and absence of paradoxical breathing pattern, they underwent a lung function evaluation and answered three questionnaires: Chronic Respiratory Questionnaire (CRQ), Modified Medical Research Council Dyspnea Scale (MMRC), and COPD Assessment Test (CAT). Then, on two consecutive days, patients performed 6MST or six-minute walk test (6MWT), in random order. Each test was performed twice, and the best performance was recorded. Also, the patient's severity was classified according to the BODE index. Inspiratory capacity measurements were performed before and after each test execution. Results: Sixteen patients (69.4 ± 11.4 years) with a mean FEV1 of 49.4 ± 9.9% predicted were included (9 females). There was a strong correlation of the performance in 6MST (number of cycles) with 6MWT (distance walked in meters) in absolute values (r = 0.87, p < 0.001) as well as with the percentage of predicted normal 6MWT (r = 0.86, p < 0.001). There was a strong correlation between the performance in 6MST with the dynamic hyperinflation (r = 0.72, p = 0.002) and a moderate correlation between 6MST with the percentage of reduction of inspiratory capacity (r = 0.68, p = 0.004). We also identified that 6MST showed moderate negative correlations with CAT (r = -0.62, p = 0.01) and BODE index (r = -0.59, p = 0.01). Conclusion: It could be concluded that 6MST is valid for evaluating functional capacity in hospitalized patients with exacerbated COPD.

Investigation of dynamic hyperinflation and its relationship with exercise capacity in children with bronchiectasis.

BACKGROUND AND AIM: Dynamic hyperinflation (DH) is a major contributor to exercise intolerance in patients with obstructive lung diseases. However, it has not been investigated in children with bronchiectasis (BE). We aimed to investigate dynamic ventilatory responses and their influence on functional exercise capacity in children with BE. METHODS: Forty children with BE (mean forced expiratory volume in 1 s [FEV1 ] = 78 ± 19%pred) were included. Six-minute walk test (6MWT) was conducted using Spiropalm 6MWT® for evaluating dynamic ventilatory responses including inspiratory capacity (IC), minute ventilation (VE), breathing reserve (BR) and respiratory rate (RR). A decrease of ≥100 ml in IC during exertion was defined as DH. Also, spirometry was performed, and peripheral muscle strength were measured. RESULTS: Twenty patients (50%) developed DH, and four patients (10%) were ventilatory limited (BR < %30) during 6MWT. There was a 176 [100-590] ml decrease in IC after exertion in patients with DH. DH did not correlate to clinical or functional indicators of the disease, except for an increase in RR (∆RR) during exertion. High ∆RR was associated with presence of DH (rpb = 0.390; p < 0.05). Clinical features, peripheral muscle strength, and Spiropalm 6MWT metrics including 6MWT distance did not differ between patients with and without DH. Univariate analysis revealed FVC% (R = 0.340), VEpeak (R = 0.565), quadriceps strength (R = 0.698) and handgrip strength (R = 0.711) were the only predictors of 6MWT distance (p < 0.05). CONCLUSION: Although DH is common in children with BE, the severity of DH is rather low and may not seem to affect functional exercise capacity. However, peripheral muscle strength was a major contributor to functional exercise capacity.

Intercostal muscle oxygenation and expiratory loaded breathing at rest: Respiratory pattern effect.

In patients with airway obstruction, an increase in breathing frequency at rest is commonly associated with a dynamic hyperinflation (DH). In such a situation, intercostal muscle oxygenation may be disturbed. This hypothesis was examined in a context of simulated airway obstruction in healthy subjects. After a control period of 5 min, twelve participants (20 ± 2 years) breathed at rest through a 20-cmH2O expiratory threshold load, either by increasing or reducing their respiratory rate (ETLF+ or ETLF). Tissue saturation index (TSI) and concentration changes in oxyhaemoglobin (oxy[Hb+Mb]) were measured as well as cardiorespiratory variables. Inspiratory capacity was decreased in ETLF+ (p < 0.001) and correlated with dyspnea. An increase in oxy[Hb+Mb] occurred in ETLF+ that was higher than in ETLF (p < 0.01). TSI was not different between conditions. In healthy subjects at rest, an increase in respiratory rate during a simulated obstruction with an expiratory threshold load resulted in paradoxical response with DH emergence while intercostal muscle oxygenation was preserved.

Sex differences in the ventilatory responses to exercise in mild to moderate obesity.

NEW FINDINGS: What is the central question of the study? What are the sex differences in ventilatory responses during exercise in adults with obesity? What is the main finding and its importance? Tidal volume and expiratory flows are lower in females when compared with males at higher levels of ventilation despite small increases in end-expiratory lung volumes. Since dyspnoea on exertion is a frequent complaint, particularly in females with obesity, careful attention should be paid to unpleasant respiratory symptoms and mechanical ventilatory constraints while prescribing exercise. ABSTRACT: Obesity is associated with altered ventilatory responses, which may be exacerbated in females due to the functional consequences of sex-related morphological differences in the respiratory system. This study examined sex differences in ventilatory responses during exercise in adults with obesity. Healthy adults with obesity (n = 73; 48 females) underwent pulmonary function testing, underwater weighing, magnetic resonance imaging (MRI), a graded exercise test to exhaustion, and two constant work rate exercise tests; one at a fixed work rate (60 W for females and 105 W for males) and one at a relative intensity (50% of peak oxygen uptake, V ̇ O 2 peak ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ ). Metabolic, respiratory and perceptual responses were assessed during exercise. Compared with males, females used a smaller proportion of their ventilatory capacity at peak exercise (69.13 ± 14.49 vs. 77.41 ± 17.06% maximum voluntary ventilation, P = 0.0374). Females also utilized a smaller proportion of their forced vital capacity (FVC) at peak exercise (tidal volume: 48.51 ± 9.29 vs. 54.12 ± 10.43%FVC, P = 0.0218). End-expiratory lung volumes were 2-4% higher in females compared with males during exercise (P < 0.05), while end-inspiratory lung volumes were similar. Since the males were initiating inspiration from a lower lung volume, they experienced greater expiratory flow limitation during exercise. Ratings of perceived breathlessness during exercise were similar between females and males at comparable levels of ventilation. In summary, sex differences in the manifestations of obesity-related mechanical ventilatory constraints were observed. Since dyspnoea on exertion is a common complaint in patients with obesity, particularly in females, exercise prescriptions should be tailored with the goal of minimizing unpleasant respiratory sensations.

Association of air pollution exposure with exercise-induced oxygen desaturation in COPD.

BACKGROUND: There is a link between exposure to air pollution and the increased prevalence of chronic obstructive pulmonary disease (COPD) and declining pulmonary function, but the association with O2 desaturation during exercise in COPD patients with emphysema is unclear. Our aims were to estimate the prevalence of O2 desaturation during exercise in patients with COPD, and determine the association of exposure to air pollution with exercise-induced desaturation (EID), the degree of emphysema, and dynamic hyperinflation (DH). METHODS: We assessed the effects of 10-year prior to the HRCT assessment and 7 days prior to the six-minute walking test exposure to particulate matter with an aerodynamic diameter of < 10 µm (PM10) or of < 2.5 µM (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in patients with emphysema in this retrospective cohort study. EID was defined as a nadir standard pulse oximetry (SpO2) level of < 90% or a delta (△)SpO2 level of ≥ 4%. Ambient air pollutant (PM2.5, PM10, O3, and NO2) data were obtained from Taiwan Environmental Protection Administration (EPA) air-monitoring stations, usually within 10 km to each participant's home address. RESULTS: We recruited 141 subjects with emphysema. 41.1% of patients with emphysema exhibited EID, and patients with EID had more dyspnea, worse lung function, more severe emphysema, more frequent acute exacerbations, managed a shorter walking distance, had DH, and greater long-term exposure to air pollution than those without EID. We observed that levels of 10-year concentrations of PM10, PM2.5, and NO2 were significantly associated with EID, PM10 and PM2.5 were associated with the severity of emphysema, and associated with DH in patients with emphysema. In contrast, short-term exposure did not have any effect on patients. CONCLUSION: Long-term exposure to ambient PM10, PM2.5 and NO2, but not O3, was associated with EID.

A randomized, crossover, placebo controlled, double-blind trial of the effects of tiotropium-olodaterol on neuromuscular performance during exercise in COPD.

Exercise intolerance in chronic obstructive pulmonary disease (COPD) is associated with dyspnea, reduced inspiratory capacity (IC) and occurs with a neuromuscular "power reserve," i.e., an acute ability to increase isokinetic locomotor power. This power reserve is associated with resting forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) suggesting that treatments to target pulmonary function may protect neuromuscular performance and extend whole body exercise in COPD. We, therefore, tested whether combination long-acting ß-agonist and muscarinic antagonist bronchodilator therapy [long-acting muscarinic antagonist (LAMA) + long-acting ß-agonist (LABA); Stiolto Respimat] would ameliorate the decline in neuromuscular performance and increase endurance time during constant power cycling at 80% peak incremental power. Fourteen patients with COPD (4 female; 64 [58, 72] yr; FEV1 67% [56%, 75%] predicted; median [25th, 75th percentile]) participated in a randomized, placebo-controlled crossover trial (NCT02845752). Pulmonary function and cardiopulmonary exercise responses were assessed before and after 1 wk of treatment, with 2 wk washout between conditions. Performance fatigue was assessed using an ∼4-s maximal isokinetic cycling effort at preexercise, isotime, and intolerance. Isotime was the shorter exercise duration of the two treatment conditions. Significance was assessed using ANOVA with treatment as fixed factor and subject as random factor. FEV1 was greater with LAMA + LABA versus placebo (1.81 [1.58, 1.98] L vs. 1.72 [1.29, 1.99] L; P = 0.006), but IC at isotime, performance fatigue at isotime, and constant power endurance time were not different between conditions (each P > 0.05). A modest (∼95 mL) increase in FEV1 following 1 wk of combination LAMA + LABA treatment did not alleviate neuromuscular performance fatigue or enhance cycle exercise tolerance in patients with mild-to-severe COPD with largely preserved "static" lung volumes.NEW & NOTEWORTHY Bronchodilation is known to increase forced expiratory volume in 1 s (FEV1) and reduce hyperinflation in COPD. In a randomized controlled trial, we investigated whether combined inhaled long-acting ß-agonist and muscarinic antagonist would alleviate maximal voluntary neuromuscular performance fatigue or enhance maximal muscle activation during cycling in patients with COPD. Despite increased FEV1, combination bronchodilator therapy did not reduce neuromuscular performance fatigue or enhance muscle activity or exercise tolerance in patients with mild-to-severe COPD.

Endotracheal Tube Size Is Associated With Mortality in Patients With Status Asthmaticus.

BACKGROUND: There is limited evidence on the clinical importance of the endotracheal tube (ETT) size selection in patients with status asthmaticus who require invasive mechanical ventilation. We set out to explore the clinical outcomes of different ETT internal diameter sizes in subjects mechanically ventilated with status asthmaticus. METHODS: This was a retrospective study of intubated and non-intubated adults admitted for status asthmaticus between 2014-2021. We examined in-hospital mortality across subgroups with different ETT sizes, as well as non-intubated subjects, using logistic and generalized linear mixed-effects models. We adjusted for demographics, Charlson comorbidities, the first Sequential Organ Failure Assessment score, intubating personnel and setting, COVID-19, and the first PaCO2 . Finally, we calculated the post-estimation predictions of mortality. RESULTS: We enrolled subjects from 964 status asthmaticus admissions. The average age was 46.9 (SD 14.5) y; 63.5% of the encounters were women and 80.6% were Black. Approximately 72% of subjects (690) were not intubated. Twenty-eight percent (275) required endotracheal intubation, of which 3.3% (32) had a 7.0 mm or smaller ETT (ETT ≤ 7 group), 16.5% (159) a 7.5 mm ETT (ETT ≤ 7.5 group), and 8.6% (83) an 8.0 mm or larger ETT (ETT ≥ 8 group). The adjusted mortality was 26.7% (95% CI 13.2-40.2) for the ETT ≤ 7 group versus 14.3% ([(95% CI 6.9-21.7%], P = .04) for ETT ≤ 7.5 group and 11.0% ([95% CI 4.4-17.5], P = .02) for ETT ≥ 8 group, respectively. CONCLUSIONS: Intubated subjects with status asthmaticus had higher mortality than non-intubated subjects. Intubated subjects had incrementally higher observed mortality with smaller ETT sizes. Physiologic mechanisms can support this dose-response relationship.

The role of inspiratory capacity and tidal flow in diagnosing exercise ventilatory limitation in Cystic Fibrosis.

BACKGROUND: Exercise ventilatory limitation conventionally defined by reduced breathing reserve (BR) may underestimate the effect of lung disease on exercise capacity in patients with mild to moderate obstructive lung diseases. OBJECTIVE: To investigate whether ventilatory limitation may be present despite a normal BR in Cystic Fibrosis (CF). METHODS: Twenty adult CF patients (age 16-58y) with a wide range of pulmonary obstruction severity completed a symptom-limited incremental exercise test on a cycle ergometer. Operating lung volumes were derived from inspiratory capacity (IC) measurement during exercise and exercise tidal flow volume loop analysis. RESULTS: six patients had a severe airway obstruction (FEV1<45% predicted) and conventional evidence of ventilatory limitation (low BR). Fourteen patients had mild to moderate-severe airway obstructive (FEV1 46-103% predicted), and a normal BR [12-62 L/min, BR% (17-40)]. However, dynamic respiratory mechanics demonstrated that even CF patients with mild to moderate-severe lung disease had clear evidence of ventilatory limitation during exercise. IC was decreased by (median) 580 ml (range 90-1180 ml) during exercise, indicating dynamic hyperinflation. Inspiratory reserve volume at peak exercise was 445 ml (241-1350 ml) indicating mechanical constraint on the respiratory system. The exercise tidal flow met or exceeded the expiratory boundary of the maximal flow volume loop over 72% of the expiratory volume (range 40-90%), indicating expiratory flow limitation. CONCLUSION: Reduced BR as a sole criterion underestimates ventilatory limitation during exercise in mild to moderate-severe CF patients. Assessment of dynamic respiratory mechanics during exercise revealed ventilatory limitation, present even in patients with mild obstruction.

Dynamic hyperinflation, chronotropic intolerance and abnormal heart rate recovery in non-severe chronic obstructive pulmonary disease patients-reflections in the mirror.

BACKGROUND: The presence of abnormal heart rate recovery (HRR) and chronotropic incompetence (CI) suggests autonomic dysfunction (AD) and is associated with diminished physical activity and increased cardio-vascular (CV) risk. AIM: Our aim is to analyse the correlation between AD and airflow obstruction - forced expiratory volume in 1s (FEV1), dynamic hyperinflation (DH) and disease prognosis - the BODE ... index (BMI; Obstruction ... FEV1;Dyspnea ... mMRC;E ... exercise capacity) in non-severe COPD patients without overt CV comorbidities. METHODS: We used cardio-pulmonary exercise testing (CPET) with 67 subjects. Inspiratory capacity (IC) manouevres were performed for DH assessment. Echocardiography was executed before CPET and 1...2min after peak exercise. Stress left ventricular diastolic dysfunction (LVDD) was assumed if stress E/e...>15.Wilkoff method calculated the metabolic-chronotropic relationship (MCR). Chronotropic incompetence (CI) and abnormal HR recovery (HRR) were determined. MAIN RESULTS: CI was detected in 44% of the mild and 65% of the moderate COPD patients. Abnormal HRR was present in 75% of the mild and 78% of the moderate COPD subjects. Multivariate regression analysis showed no association between FEV1, CPET parameters, BODE index, stress LVDD and AD. DH was the only independent predictor for both abnormal HRR and CI. CONCLUSION: Evaluation of AD during incremental CPET unravels lung hyperinflation as a potential mechanism of attenuated HR response and diminished physical activity in non-severe COPD free of overt CV comorbidities. This multifaceted approach to dyspnea may facilitate the discrimination of its pathogenesis and improve its proper clinical management.

Ventilatory constraint is more severe in walking than cycling in patients with COPD.

Due to its effectivity in assessing functional capacity and adding prognostic information to the staging of chronic obstructive pulmonary disease (COPD) patients, the 6-min walk test (6MWT) is extensively used in clinical evaluation. Currently, there is little information about the physiological response this test elicits in patients, especially when compared to cardiopulmonary exercise test (CPET). The aim of the study was to compare ventilatory and metabolic responses between these tests commonly used for the assessment of clinical outcome. A group of 20 patients with moderate to very severe COPD were tested for their pulmonary function (flow-volume curve, static lung volumes), occlusion mouth pressures and breath-by-breath measurement of flow, volumes, and oxygen (O2) and carbon dioxide (CO2) concentration during the 6MWT and CPET. All parameters measured during both exercise tests were assessed over the throughout of the tests and compared between each other at specified time points. Serially measured inspiratory vital capacity (IVC) decreased more rapidly and extensively during the walk-test (p â€‹< â€‹0,0001). This was accompanied by a limited increase in tidal volume (VT) and minute ventilation (VE), which were significantly lower in the course of the 6MWT (p â€‹= â€‹0,0003 and p â€‹= â€‹0,0097, respectively). We also noticed a significant decrease in hemoglobin oxygen saturation (SpO2) during the 6MWT which was correlated to percent decrease in IVC (p â€‹= â€‹0,0206). Over the course of the 6MWT, oxygen consumption (VO2) and VT reached plateau within 2 â€‹min, while carbon dioxide production (VCO2) and VE within 3 â€‹min. During CPET, VO2, VCO2 and VE rose continuously, while VT reached plateau within 4 â€‹min. The 6MWT seems to be a rather endurance-based test associated with more pronounced dynamic lung hyperinflation and mechanical constraint of ventilation in comparison to cycling.

Predictors of exercise-induced bronchoconstriction in subjects with mild asthma.

BACKGROUND: Physical effort is capable of triggering airway obstruction in asthmatics, the so-called exercise-induced bronchoconstriction in asthma (EIBa). This study was performed in subjects with mild persistent asthma, aiming to find predictors for developing EIBa. METHODS: In 20 subjects with mild asthma, measurements of baseline functional respiratory parameters and airways responsiveness by a methacholine challenge were obtained on the first day. A maximal, symptom-limited incremental cardiopulmonary exercise test (CPExT) was performed the day after, with subsequent, repeated maneuvers of maximal full forced expiration to monitor the FEV1 change at 1,3,5,7,10 and 15 min after the end of the exercise. RESULTS: 19 subjects completed the two-days protocol. No functional parameters both at rest and during effort were useful to predict EIBa after stopping exercise. In asthmatics with EIBa, mean Inspiratory Capacity (IC) did not increase with increasing ventilatory requirements during CPExT because 6 of them (50%) displayed dynamic pulmonary hyperinflation (DH), as documented by their progressive increase of end-expiratory lung volume. This subgroup, showing earlier post-exercise FEV1 fall, had significantly lower forced mean expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) at rest (p < 0.05) and higher airways responsiveness, expressed as PD20FEV1 (p < 0.05) as compared with other asthmatics with EIBa. CONCLUSIONS: No functional respiratory parameters seem to predict EIBa in mild asthmatics. However, in those with EIBa, a subgroup developed DH during exercise, and this was associated with a baseline reduced forced expiratory flow rates at lower lung volumes and higher airway hyperresponsiveness, suggesting a prominent small airways impairment.