LAMA improve tissue oxygenation more than LABA in patients with COPD.

Background The effect of bronchodilators is mainly assessed with forced expiratory volume in 1s (FEV1) in COPD. Their impact on oxygenation and lung periphery is less known. Objectives To compare the action of long-acting ß2-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD, considering their impact on proximal and peripheral ventilation as well as lung perfusion. Methods FEV1, Helium slope (SHe) from a single-breath washout test (SHe decrease reflecting a peripheral ventilation improvement), frequency dependence of resistance (R5-R19), area under reactance (AX), lung capillary blood volume (Vc) from double diffusion (DLNO/DLCO) and transcutaneous oxygenation (TcO2) were measured before and 2 hours post-LABA (day 1) and LAMA (day 3) in 30 COPD patients (FEV1 54±18% pred; GOLD A 31%/B 48%/E 21%) after 5-7 days of washout, respectively. Results TcO2 increased more (p=0.03) after LAMA (11±12%from baseline, p<0001) compared to LABA (4±11%, p=0.06) despite a lower FEV1 increase (p=0.03) and similar SHe (p=0.98), AX (p=0.63) and R5-R19 decreases (p=0.37). TcO2 and SHe changes were negatively correlated (r=-0.47, p=0.01) after LABA, not after LAMA (r=0.10, p=0.65). DLNO/DLCO decreased and Vc increased after LAMA (p=0.04; p=0.01, respectively) but not after LABA (p=0.53; p=0.24). Conclusion LAMA significantly improved tissue oxygenation in COPD patients, while only a trend was observed with LABA. The mechanisms involved may differ between both drugs: LABA increased peripheral ventilation while LAMA increased lung capillary blood volume. Should oxygenation differences persist over time, LAMA could arguably become the first therapeutic choice in COPD.

The Impact of Airway Obstruction on Feno Values in Asthma Patients.

BACKGROUND: Exhaled nitric oxide (Feno) is used as a marker of type-2 airway inflammation in asthma management. Studies with airway challenges demonstrated that a reduction in airway caliber decreases Feno levels. OBJECTIVE: To evaluate the impact of airway caliber reduction occurring spontaneously in patients with asthma on Feno values in daily clinical practice. METHODS: In this post hoc analysis, Feno, FEV1, and asthma control questionnaire scores were recorded on each visit for 120 (1073 visits) adult patients with asthma. Blood eosinophils were measured intermittently. The intraindividual relationship between Feno and FEV1 was evaluated via a linear mixed model. The determinants of the individual mean Feno were measured by a stepwise multivariate linear model including individual mean FEV1, inhaled corticosteroid dose, asthma control questionnaire score, and blood eosinophils. RESULTS: Variations in the negative Feno-FEV1 relationship within individuals at different times were significantly determined by the individual's mean FEV1. This relationship did not hold for individuals above the 75th and below the 25th quartiles. The best explanatory variables for individual mean Feno were FEV1 (+4.3 parts per billion/10%pred) and blood eosinophil count (+1 part per billion per 100 cells/mm3). DISCUSSION: In the presence of variable degrees of heterogeneous patterns of airway inflammation, airway caliber is shown to be an independent and significant determinant of Feno when measured in patients with asthma. We would propose a +4-parts-per-billion correction factor to the measured Feno value for each 10% reduction below 100% predicted FEV1. Doing this should improve the rigor of interpretation of Feno as an indicator of type-2 inflammation in patients with low FEV1.

Nutrition evaluation and management of critically ill patients with COVID-19 during post-intensive care rehabilitation.

BACKGROUND: Among hospitalized patients with coronavirus disease 2019 (COVID-19), up to 12% may require intensive care unit (ICU) management. The aim of this prospective cohort study is to assess nutrition status and outcome in patients with COVID-19 following ICU discharge. METHODS: Patients requiring a minimum of 14 days' stay in the ICU with mechanical ventilation were included. Nutrition status was assessed at inclusion (ICU discharge) and follow-up (after 15, 30, and 60 days). All patients had standardized medical nutrition therapy with defined targets regarding energy (30 kcal/kg/d) and protein intake (1.5 g/kg/d). RESULTS: Fifteen patients were included (67% males); the median age was 60 (33-75) years old. Body mass index at ICU admission was 25.7 (IQR, 24-31) kg/m². After a median ICU stay of 33 (IQR, 26-39) days, malnutrition was present in all patients (11.3% median weight loss and/or low muscle mass based on handgrip strength measurement). Because of postintubation dysphagia in 60% of patients, enteral nutrition was administered (57% nasogastric tube; 43% percutaneous endoscopic gastrostomy). After 2 months, a significant improvement in muscle strength was observed (median handgrip strength, 64.7% [IQR, 51%-73%] of the predicted values for age vs 19% [IQR, 4.8%-28.4%] at ICU discharge [P < 0.0005]), as well as weight gain of 4.3 kg (IQR, 2.7-6.7 kg) (P < 0.0002). CONCLUSIONS: Critically ill patients with COVID-19 requiring ICU admission and mechanical ventilation have malnutrition and low muscle mass at ICU discharge. Nutrition parameters improve during rehabilitation with standardized medical nutrition therapy.

Exploring the sites and kinetics of bronchodilator response to ß-2 agonists in asthma.

We previously documented, in patients with asthma, three different profiles of bronchodilation induced by short-acting ß-2 mimetics (SABA), characterized by dilation up to central, preacinar, and intra-acinar airways assessed by ventilation distribution tests and associated with no change, increase, and decrease of fractional exhaled nitric oxide concentration (FENO), respectively. To investigate the dynamics of these profiles over the entire SABA action period, assuming that bronchodilation of proximal and peripheral airways could exhibit varying kinetics due to differences in the distribution of ß-2 receptors in both the central and peripheral human airways. FENO, forced expired volume in one second (FEV1), and the slope (S) of He and SF6 phase III (single-breath test) were measured in asthma patients before, and up to 6 h after SABA inhalation (salbutamol 400 µg). SHe and SSF6 decrease reflects pre- and intra-acinar obstruction relief, respectively. Thirty patients with asthma (12F/18M, aged 45 ± 18 yr) were divided into groups with positive (NO+, n = 9), negative (NO-, n = 11), and no (NO=, n = 10) FENO acute change. In the NO- group, FEV1 increased for up to 4 h, whereas FENO, SHe, and SF6 decreased in the early phase only. In stark contrast, in the NO+ group, FEV1 increased in the early phase only whereas the FENO increase and the SHe decrease lasted for up to 4 h. This study documents various profiles of SABA-induced bronchodilation in patients with asthma, differing both by sites and dynamics of the bronchodilator process. So, detailed understanding of the bronchodilator effect of ß2-agonists in asthma should not solely be limited to studying their impact on FEV1.NEW & NOTEWORTHY FEV1 increase usually observed after the inhalation of short-acting ß2-agonists in asthma patients tends to involve peripheral airways. This study shows that the heterogeneity of responses to short-acting ß2-agonists in asthma not only involves distinct sites of bronchodilation, but also distinct sequences between these sites. This indicates that a detailed understanding of the bronchodilator effect of ß2-agonists in asthma should not be limited to studying its early impact on FEV1.

COPD patients with peripheral airway obstruction reversibility identified by exhaled nitric oxide.

RATIONALE: Besides its role as an inflammatory marker in asthma, fractional exhaled nitric oxide (FENO) provides information on the extent of the airway obstruction process through evaluating its change after bronchodilation. OBJECTIVE: To investigate whether FENO change after bronchodilation can identify different sites of airway obstruction in COPD patients. METHODS: FENO, FEV1 and the slopes (S) of the alveolar plateau of the single breath washout test (SBWT) were measured in 61 stable COPD patients (FEV1 34.5% predicted) before and after the inhalation of 400 µg salbutamol. SBWT used Helium (He), and sulfur-hexafluoride (SF6). Obstruction relief occurring in pre-acinar and intra-acinar small airways is expected to decrease SHe and SSF6, respectively. Indices changes (Δ) after bronchodilation were expressed as a percentage of pre-bronchodilation values. RESULTS: FENO stability (∣ΔFENO∣ ≤ 11%) was observed in 19 patients [-2.7(6.7)%] [mean (SD)] (NO = group); ΔFENO > 11% [+37.4(27.7)%] in 20 patients (NO+ group) and ΔFENO < -11% in 22 patients [-31.2(9.8)%] (NO- group). A similar ΔFEV1 (p = 0.583; [+9.4(9.6)%]) was found in the three groups. In NO = and NO+ groups, neither SHe nor SSF6 changed; in NO- both SHe [-12.4(27.5)%, p = 0.007] and SSF6 [-20.2(20.4)%, p < 0.001] significantly decreased. CONCLUSION: Different patterns of FENO response to ß 2-agonists were observed in COPD most likely depending on the extent of the dilation process. A profile of airway obstruction with an extensive ß 2-agonist response down to lung periphery is identified by FENO reduction after acute bronchodilation in 30% of COPD patients. The clinical relevance of this profile requires further investigation.

Short and long-term effects of pulmonary rehabilitation in interstitial lung diseases: a randomised controlled trial.

BACKGROUND: Few data are available on the long-term effect of pulmonary rehabilitation (PR) and on long PR programs in interstitial lung diseases (ILD). We aimed to evaluate the effects of PR on exercise capacity (6-Minute Walking Distance, 6MWD; Peak Work Rate, Wmax), quality of life (St George's Respiratory Questionnaire, SGRQ), quadriceps force (QF) and objectively measured physical activity in ILD after the 6-month PR-program and after 1 year. METHODS: 60 patients (64 ± 11 years; 62% males; 23% with IPF) were randomly assigned to receive a 6 month-PR program or usual medical care. RESULTS: Exercise capacity, quality of life and muscle force increased significantly after the program as compared to control (mean,95%CI[ll to ul]; 6MWD + 72,[36 to 108] m; Wmax 19, [8 to 29]%pred; SGRQ - 12,[- 19 to - 6] points; QF 10, [1 to 18] %pred). The gain was sustained after 1 year (6MWD 73,[28 to 118] m; Wmax 23, [10 to 35]%pred; SGRQ - 11,[- 18 to - 4] points; QF 9.5, [1 to 18] %pred). Physical activity did not change. CONCLUSIONS: PR improves exercise tolerance, health status and muscle force in ILD. The benefits are maintained at 1-year follow-up. The intervention did not change physical activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT00882817 .

Rehabilitation in patients with radically treated respiratory cancer: A randomised controlled trial comparing two training modalities.

INTRODUCTION: The evidence on the effectiveness of rehabilitation in lung cancer patients is limited. Whole body vibration (WBV) has been proposed as an alternative to conventional resistance training (CRT). METHODS: We investigated the effect of radical treatment (RT) and of two rehabilitation programmes in lung cancer patients. The primary endpoint was a change in 6-min walking distance (6MWD) after rehabilitation. Patients were randomised after RT to either CRT, WBVT or standard follow-up (CON). Patients were evaluated before, after RT and after 12 weeks of intervention. RESULTS: Of 121 included patients, 70 were randomised to either CON (24), CRT (24) or WBVT (22). After RT, 6MWD decreased with a mean of 38m (95% CI 22-54) and increased with a mean of 95m (95% CI 58-132) in CRT (p<0.0001), 37m (95% CI -1-76) in WBVT (p=0.06) and 1m (95% CI -34-36) in CON (p=0.95), respectively. Surgical treatment, magnitude of decrease in 6MWD by RT and allocation to either CRT or WBVT were prognostic for reaching the minimally clinically important difference of 54m increase in 6MWD after intervention. CONCLUSIONS: RT of lung cancer significantly impairs patients' exercise capacity. CRT significantly improves and restores functional exercise capacity, whereas WBVT does not fully substitute for CRT.

Modification of COPD presentation during the last 25 years.

During the last decades progress has been made in the treatment of Chronic Obstructive Pulmonary Disease (COPD). We compared a random sample of patients admitted for an exacerbation in the period 2001-2005 (n = 101), with a random sample of patients hospitalized for the same reason in the period 1980-1984 (n = 51). Patients of the 2001-2005 cohort had a lower FEV1 (48 ± 3 vs. 41 ± 2% predicted, p = 0.01) for similar mean age, gender and body- mass index when compared to the historical sample. Co-morbidities, according to the Charlson's index, were more prevalent in the 2001-2005 cohort compared to the 1980-1984 cohort, with a reduction of hemoglobin (13.9 ± 0.2 gr/dl vs. 14.9 ± 0.2, p < 0.01) and higher prevalence of anemia in the most recent cohort. We found an increase in the use of cardiovascular drugs and respiratory medications over time with exception for the long-term use of oxygen. Despite lower FEV1 and more prevalent co-morbidities, no difference in length of hospitalization (13.6 ± 1.4 days vs. 12.7 ± 0.7 days, p = 0.52) and 30 months survival post-exacerbation was noted (66.6% vs. 69.3%, p = 0.85). Over the course of 20 years, the presentation of COPD patients admitted for an exacerbation seems to be changed towards a more severe phenotype with lower FEV1 and more co-morbidities. As the length of hospitalization and the overall survival were not different between the two samples, a currently improved management of COPD can be hypothesized.