Respiratory Muscle Strength Is Related to Handgrip Performance in Community-Dwelling Persons Aged 80+ from the BUTTERFLY Study.

INTRODUCTION: This study aimed to evaluate the association of respiratory muscle strength with sarcopenia and its indicators in the oldest old. METHODS: Maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and sarcopenia-related factors (handgrip strength and appendicular lean mass) were evaluated in a cohort of n = 286 (45.5% female) non-frail, community-dwelling persons aged 83.6 ± 3.0 years (age range 80-97 years). RESULTS: The sample presented a sarcopenia prevalence of 32.2%. Sarcopenic subjects showed comparable MIP and MEP as non-sarcopenic ones (female: MIP 43.9 ± 18.9 vs. 50.3 ± 19.5, p = 0.053; MEP 63.0 ± 23.0 vs. 69.2 ± 19.1, p = 0.067; male: MIP, 65.1 ± 24.4 vs. 64.4 ± 23.9, p = 0.433; MEP 87.7 ± 33.3 vs. 93.8 ± 30.9, p = 0.124). Statistically significant but very low associations were found between grip strength and MIP (r = 0.193 for male, p < 0.05 and r = 0.257 for female participants, p < 0.01) and MEP (r = 0.200 for male, p < 0.01 and r = 0.191 for female participants, p < 0.05). Lean mass was significantly correlated to MIP and MEP in female (r = 0.253, p < 0.01 and r = 0.343, p < 0.01, respectively), whereas this association was not found in male participants. Grip strength was the only statistically significant predictor of MEP (r2 = 0.212, p < 0.001), while MIP was independently predicted by age, male sex, and grip strength (r2 = 0.177, p < 0.001). CONCLUSIONS: Peripheral muscle strength is a statistically significant, albeit weak predictor for respiratory muscle strength in well-functioning, community-dwelling persons aged 80+. When confronted to a low grip strength, one should be aware of concomitant respiratory muscle weakness, as this is a known risk factor for atelectasis and pneumonia. Given the relatively low association with handgrip strength, respiratory muscle strength testing might be indicated.

European Respiratory Society short guidelines for the use of as-needed ICS/formoterol in mild asthma

Recent clinical trials of as-needed fixed-dose combination of inhaled corticosteroid (ICS)/formoterol have provided new evidence that may warrant a reconsideration of current practice. A Task Force was set up by the European Respiratory Society to provide evidence-based recommendations on the use of as-needed ICS/formoterol as treatment for mild asthma. The Task Force defined two questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The Task Force utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The Task Force suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting ß2-antagonist (SABA) and that adolescents with mild asthma use either as-needed ICS/formoterol or ICS maintenance treatment plus as-needed SABA (conditional recommendation; low certainty of evidence). The recommendation for adults places a relatively higher value on the reduction of systemic corticosteroid use and the outcomes related to exacerbations, and a relatively lower value on the small differences in asthma control. Either treatment option is suggested for adolescent patients as the balance is very close and data more limited. The Task Force recommends that adult and adolescent patients with mild asthma use as-needed ICS/formoterol instead of as-needed SABA (strong recommendation; low certainty of evidence). This recommendation is based on the benefit of as-needed ICS/formoterol in mild asthma on several outcomes and the risks related to as-needed SABA in the absence of anti-inflammatory treatment. The implementation of this recommendation is hampered in countries (including European Union countries) where as-needed ICS/formoterol is not approved for mild asthma.

European Respiratory Society short guidelines for the use of as-needed ICS/formoterol in mild asthma.

Recent clinical trials of as-needed fixed-dose combination of inhaled corticosteroid (ICS)/formoterol have provided new evidence that may warrant a reconsideration of current practice. A Task Force was set up by the European Respiratory Society to provide evidence-based recommendations on the use of as-needed ICS/formoterol as treatment for mild asthma. The Task Force defined two questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. The Task Force utilised the outcomes to develop recommendations for a pragmatic guideline for everyday clinical practice. The Task Force suggests that adults with mild asthma use as-needed ICS/formoterol instead of regular ICS maintenance treatment plus as-needed short-acting ß2-antagonist (SABA) and that adolescents with mild asthma use either as-needed ICS/formoterol or ICS maintenance treatment plus as-needed SABA (conditional recommendation; low certainty of evidence). The recommendation for adults places a relatively higher value on the reduction of systemic corticosteroid use and the outcomes related to exacerbations, and a relatively lower value on the small differences in asthma control. Either treatment option is suggested for adolescent patients as the balance is very close and data more limited. The Task Force recommends that adult and adolescent patients with mild asthma use as-needed ICS/formoterol instead of as-needed SABA (strong recommendation; low certainty of evidence). This recommendation is based on the benefit of as-needed ICS/formoterol in mild asthma on several outcomes and the risks related to as-needed SABA in the absence of anti-inflammatory treatment. The implementation of this recommendation is hampered in countries (including European Union countries) where as-needed ICS/formoterol is not approved for mild asthma.

Lung Restriction in Patients With Breast Cancer After Hypofractionated and Conventional Radiation Therapy: A 10-Year Follow-up.

PURPOSE: Previous studies in patients with breast cancer have shown acute radiation therapy-induced reductions of pulmonary diffusing capacity, essentially owing to lung volume restriction. We aimed to assess the long-term effect of 2 radiation therapy regimens, which differed in terms of radiation technique and dose fractionation, on lung function. METHODS AND MATERIALS: From a randomized controlled trial comparing conventional 3-dimensional conformal radiation therapy (CR) and hypofractionated tomotherapy (TT), 84 patients with breast cancer (age at inclusion 54 ± 10 [standard deviation] years) could be assessed at baseline, after 3 months, and after 1, 2, 3, and 10 years. Measurements included forced vital capacity, total lung capacity (TLC), and diffusing capacity (TLco). RESULTS: Radiation therapy-induced lung function changes over 10 years (Δ) were similar for both treatment arms, and in a patient subgroup with negligible history of respiratory disease or smoking (n = 57) these averaged: Δ forced vital capacity = -13 (± 9) percent predicted; ΔTLco = -14 (± 12) percent predicted; and ΔTLC = -11 (± 9) percent predicted. The only significant correlation was between V20 (lung volume exposed to dose exceeding 20 Gy) and ΔTLco (rho = -0.36; P = .007). In this subgroup, as well as in the entire patient cohort, the incurred pulmonary restriction in terms of TLC and TLco showed a greater decline at 3 months for CR versus TT. However, at 10 years, no significant difference could be detected between CR and TT (P = .9 for TLC and P = .2 for TLco in the entire patient cohort). Of the patients with normal TLC and TLco at baseline (ie, above lower limits of normal), respectively 94% and 96% were still normal 10 years later. CONCLUSIONS: In women with breast cancer, conventional 3-dimensional conformal radiation therapy and hypofractionated tomotherapy induce similar restrictive lung patterns during the course of a 10-year period, despite some treatment-dependent differences in the first 3 months. The large majority of women with normal lung function at baseline maintained a normal lung function status 10 years after radiation therapy, irrespective of treatment arm.

European Respiratory Society Guidelines for the Diagnosis of Asthma in Adults.

Although asthma is very common affecting 5-10% of the population, the diagnosis of asthma in adults remains a challenge in the real world that results in both over- and under-diagnosis. A task force (TF) was set up by the European Respiratory Society to systematically review the literature on the diagnostic accuracy of tests used to diagnose asthma in adult patients and provide recommendation for clinical practice.The TF defined eight PICO (Population, Index, Comparator, and Outcome) questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach, The TF utilised the outcomes to develop an evidenced-based diagnostic algorithm, with recommendations for a pragmatic guideline for everyday practice that was directed by real-life patient experiences.The TF support the initial use of spirometry followed, and if airway obstruction is present, by bronchodilator reversibility testing. If initial spirometry fails to show obstruction, further tests should be performed in the following order: FeNO, PEF variability or in secondary care, bronchial challenge. We present the thresholds for each test that are compatible with a diagnosis of asthma in the presence of current symptoms.The TF reinforce the priority to undertake spirometry and recognise the value of measuring blood eosinophils and serum IgE to phenotype the patient. Measuring gas trapping by body plethysmography in patients with preserved FEV1/FVC ratio deserves further attention. The TF draw attention on the difficulty of making a correct diagnosis in patients already receiving inhaled corticosteroids, the comorbidities that may obscure the diagnosis, the importance of phenotyping, and the necessity to consider the patient experience in the diagnostic process.

How to Choose the Right Inhaler Using a Patient-Centric Approach?

There are many different inhaler devices and medications on the market for the treatment of asthma and chronic obstructive pulmonary disease, with over 230 drug-delivery system combinations available. However, despite the abundance of effective treatment options, the achieved disease control in clinical practice often remains unsatisfactory. In this context, a key determining factor is the match or mismatch of an inhalation device with the characteristics or needs of an individual patient. Indeed, to date, no ideal device exists that fits all patients, and a personalized approach needs to be considered. Several useful choice-guiding algorithms have been developed in the recent years to improve inhaler-patient matching, but a comprehensive tool that translates the multifactorial complexity of inhalation therapy into a user-friendly algorithm is still lacking. To address this, a multidisciplinary expert panel has developed an evidence-based practical treatment tool that allows a straightforward way of choosing the right inhaler for each patient.

Peripheral lung effect of elexacaftor/tezacaftor/ivacaftor in adult cystic fibrosis.

Despite being an important patient group, adult cystic fibrosis patients with an FEV1 below 40%predicted have been excluded from clinical trials with elexacaftor/tezacaftor/ivacaftor. We conducted a real-life 3 months follow-up study in 14 adult CF patients (median FEV1 34%predicted) demonstrating significant treatment effects in terms of FEV1 (an increase of 12%predicted at 4 weeks, remaining stable thereafter). Corresponding decreases in lung clearance index LCI (by 31%predicted, down from baseline 247%predicted) and ventilation heterogeneity in the acinar compartment (Sacin) (by 411%predicted, down from baseline 798%predicted) suggest a distinct peripheral lung effect. One patient had intermittent treatment interruptions because of drug-induced liver injury. Our real-life data confirm that treatment with elexacaftor/tezacaftor/ivacaftor is effective in severely obstructive patients, and this is the first study to show time evolution of ventilation distribution improvement, pointing to the peripheral lung as the main site of treatment effect.

Evolution of lung function and chest CT 6 months after COVID-19 pneumonia: Real-life data from a Belgian University Hospital.

INTRODUCTION: Most post COVID-19 follow-up studies are limited to a follow-up of 3 months. Whether a favorable evolution in lung function and/or radiological abnormalities is to be expected beyond 3 months is uncertain. MATERIALS AND METHODS: We conducted a real-life follow-up study assessing the evolution in lung function, chest CT and ventilation distribution between 10 weeks and 6 months after diagnosis of COVID-19 pneumonia. RESULTS: Seventy-nine patients were assessed at 6 months of whom 63 had chest CT at both follow-up visits and 46 had multiple breath washout testing to obtain lung clearance index (LCI). The study group was divided into a restrictive (n = 39) and a non-restrictive subgroup (n = 40) based on TLC z-score. Restriction was associated with a history of intubation, neuromuscular blockade use and critical illness polyneuropathy. Restriction significantly improved over time, but was not resolved by 6 months (median TLC z-score of -2.2 [IQR: -2.7; -1.5] at 6 months versus -2.7 [IQR: -3.1; -2.1] at 10 weeks). LCI did not evolve between both follow-up visits. Symptoms and chest CT score improved irrespective of restriction. CONCLUSION: We observed a disconnect between the improvement of COVID-19 related symptoms, chest CT lesions, and corresponding lung function. While CT imaging is almost normalized at 6 months, a further reduction of pulmonary restriction may be hoped for beyond 6 months in those patients showing restriction at their first follow-up visit.

Peak In- and Expiratory Flow Revisited: Reliability and Reference Values in Adults.

BACKGROUND: While peak in- and expiratory flow rates offer valuable information for diagnosis and monitoring in respiratory disease, these indices are usually considered too variable to be routinely used for quantification in clinical practice. OBJECTIVES: The aim of the study was to obtain reproducible measurements of maximal inspiratory flow rates and to construct reference equations for peak in- and expiratory flows (PIF and PEF). METHOD: With coaching for maximal effort, 187 healthy Caucasian subjects (20-80 years) performed at least 3 combined forced inspiratory and expiratory manoeuvres, until at least 2 peak inspiratory flow measurements were within 10% of each other. The effect on PIF preceded by a slow expiration instead of a forced expiration and PIF repeatability over 3 different days was also investigated in subgroups. Reference values and limits of normal for PIF, mid-inspiratory flow, and PEF were obtained according to the Lambda-Mu-Sigma statistical method. RESULTS: A valid PIF could be obtained within 3.3 ± 0.6(SD) attempts, resulting in an overall within-test PIF variability of 4.6 ± 3.2(SD)%. A slow instead of a forced expiration prior to forced inspiration resulted in a significant (p < 0.001) but small PIF increase (2.5% on average). Intraclass correlation coefficient for between-day PIF was 0.981 (95% CI: 0.960-0.992). Over the entire age range, inter-subject PIF variability was smaller than in previous reports, and PIF could be predicted based on its determinants gender, age, and height (r2 = 0.53). CONCLUSIONS: When adhering to similar criteria for the measurement of effort-dependent portions of inspiratory and expiratory flow-volume curves, performed according to current ATS/ERS standards, it is possible to obtain reproducible PIF and PEF values for use in routine clinical practice.

Ventilation heterogeneity in smokers: role of unequal lung expansion and peripheral lung structure.

Smoking-induced ventilation heterogeneity measured at the mouth via established washout indices [lung clearance index (LCI) and alveolar mixing efficiency (AME)] potentially results from unequal expansion, which can be quantified by computer tomography (CT), and structural changes down to the lung periphery, characterized by CT parametric response mapping indices [percentage of lung affected by functional small airway disease (PRMfSAD) and emphysema (PRMEmph)]. By combining CT imaging and nitrogen (N2) washout tests in smokers, we specifically examined the roles of unequal lung expansion and peripheral structure. We first extracted three-dimensional maps of local lung expansion from registered inspiratory/expiratory CT images in 50 smokers (GOLD 0-IV) to compute for each smoker the theoretical N2 washout concentration curve solely attributable to unequal local expansion. By a head-on comparison with washout N2 concentrations measured at the mouth in the same smokers supine, we observed that 1) LCI increased from 4.8 ± 0.2 (SD) to 6.6 ± 0.8 (SD) due to unequal lung expansion alone and further increased to 9.0 ± 1.5 (SD) independent of local expansion and 2) AME decreased (from 100% by definition) to 95 ± 2 (SD)% due to unequal expansion alone and further decreased to 75 ± 7(SD)% independent of local expansion. In a multiple regression between the washout indices and CT-derived PRMfSAD and PRMEmph, LCI was related to PRMfSAD (r = +0.58; P < 0.001), whereas AME was related to both PRMfSAD (rpartial = -0.44; P = 0.002) and PRMEmph (rpartial = -0.31; P = 0.033), in line with AME being dominated by alterations in peripheral structure. We conclude that smokers showing an increased LCI without corresponding AME decrease are predominantly affected by unequal lung expansion, whereas an AME decrease with a commensurate LCI increase indicates a smoking-induced alteration of peripheral structure.NEW & NOTEWORTHY A head-on comparison between imaging and multiple breath washout in supine smokers shows that computer tomography-measured unequal local lung expansion accounts for 50% or less of smoking-induced increase in ventilation heterogeneity. The contributions from unequal lung expansion and peripheral structure to the two main washout indices also explain their respective association with parametric response mapping indices.

Aligning Lung Function Equipment and Reference Values in Adults.

BACKGROUND: When introducing new equipment or reference equations into the lung function laboratory, systematic z-score deviations could arise due to local differences in population or equipment. OBJECTIVE: To propose a workable method for aligning reference equations with lung function equipment. METHOD: Using two cases of equipment transition in our laboratory as a test case, we first performed lung function testing after the transition, on a control group of 40 normal young adults (20 male/20 female; 20-30 years old). For those indices with an average z-score in excess of ±0.5, adapted reference values were obtained by an offset or scaling factor on the M coefficient with the so-called lambda-mu-sigma (LMS) method recommended by the Global Lung Function Initiative, and the z-scores were computed again. RESULTS: Following a transition involving instrumental dead space reduction, the lung clearance index was predictably reduced, resulting in a mean (±SD) z-score of -1.9 (±1.1) in the control group; by adapting the reference values with an offset on M, the z-score became -0.1 (±1.1). Applying the same method to a transition of standard lung function equipment, the z-scores became centered around zero in the control group, but also became properly aligned in a test group of 81 other subjects spanning a wider age range (20-80 years). CONCLUSIONS: We proposed and verified a method for aligning local equipment with reference values obtained elsewhere, or following a local change in equipment. The key is to measure a relatively small young adult group, identifying those lung function indices that need adaptation based on z-scores, in order to then obtain laboratory-specific reference values that can be applied over the entire age range.

The quantitative link of lung clearance index to bronchial segments affected by bronchiectasis.

In adult patients with cystic fibrosis (CF), the lung clearance index (LCI) derived from the multiple breath washout relates to both acinar and conductive ventilation heterogeneity. The latter component predicts an association between LCI and the number of bronchial segments affected by bronchiectasis. Here, we experimentally demonstrated this association in patients with CF, and also examined an ancillary group of patients with non-CF bronchiectasis. We conclude that lung disease severity in terms of number of bronchial segments results in an associated LCI increase, likely constituting a portion of LCI that cannot be reversed by treatment in patients with CF lung disease.

Inhaled Aerosol Distribution in Human Airways: A Scintigraphy-Guided Study in a 3D Printed Model.

BACKGROUND: While it is generally accepted that inertial impaction will lead to particle loss as aerosol is being carried into the pulmonary airways, most predictive aerosol deposition models adopt the hypothesis that the inhaled particles that remain airborne will distribute according to the gas flow distribution between airways downstream. METHODS: Using a 3D printed cast of human airways, we quantified particle deposition and distribution and visualized their inhaled trajectory in the human lung. The human airway cast was exposed to 6 µm monodisperse, radiolabeled aerosol particles at distinct inhaled flow rates and imaged by scintigraphy in two perpendicular planes. In addition, we also imaged the distribution of aerosol beyond the airways into the five lung lobes. The experimental aerosol deposition patterns could be mimicked by computational fluid dynamic (CFD) simulation in the same 3D airway geometry. RESULTS: It was shown that for particles with a diameter of 6 µm inhaled at flows up to 60 L/min, the aerosol distribution over both lungs and the individual five lung lobes roughly followed the corresponding distributions of gas flow. While aerosol deposition was greater in the main bronchi of the left versus right lung, distribution of deposited and suspended particles toward the right lung exceeded that of the left lung. The CFD simulations also predict that for both 3 and 6 µm particles, aerosol distribution between lung units subtending from airways in generation 5 did not match gas distribution between these units and that this effect was driven by inertial impaction. CONCLUSIONS: We showed combined imaging experiments and CFD simulations to systematically study aerosol deposition patterns in human airways down to generation 5, where particle deposition could be spatially linked to the airway geometry. As particles are negotiating an increasing number of airways in subsequent branching generations, CFD predicts marked deviations of aerosol distribution with respect to ventilation distribution, even in the normal human lung.

Mild Lung Restriction in Breast Cancer Patients After Hypofractionated and Conventional Radiation Therapy: A 3-Year Follow-Up.

PURPOSE: To assess the effect of radiation therapy on lung function over the course of 3 years. METHODS AND MATERIALS: Evolution of restrictive and obstructive lung function parameters was investigated in 108 breast cancer participants in a randomized, controlled trial comparing conventional radiation therapy (CR) and hypofractionated tomotherapy (TT) (age at inclusion ranging 32-81 years). Spirometry, plethysmography, and hemoglobin-corrected diffusing capacity were assessed at baseline and after 3 months and 1, 2, and 3 years. Natural aging was accounted for by considering all lung function parameters in terms of percent predicted values using the most recent reference values for women aged up to 80 years. RESULTS: In the patients with negligible history of respiratory disease or smoking (n=77), the greatest rate of functional decline was observed during the initial 3 months, this acute decrease being more marked in the CR versus the TT arm. During the remainder of the 3-year follow-up period, values (in terms of percent predicted) were maintained (diffusing capacity) or continued to decline at a slower rate (forced vital capacity). However, the average decline of the restrictive lung function parameters over a 3-year period did not exceed 9% predicted in either the TT or the CR arm. Obstructive lung function parameters remained unaffected throughout. Including also the 31 patients with a history of respiratory disease or more than 10 pack-years showed a very similar restrictive pattern. CONCLUSIONS: In women with breast cancer, both conventional radiation therapy and hypofractionated tomotherapy induce small but consistent restrictive lung patterns over the course of a 3-year period, irrespective of baseline respiratory status or smoking history. The fastest rate of lung function decline generally occurred in the first 3 months.

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults.

Monitoring of chronic lung disease requires reference values of lung function indices, including putative markers of small airway function, spanning a wide age range.We measured spirometry, transfer factor of the lung for carbon monoxide (TLCO), static lung volume, resistance and ventilation distribution in a healthy population, studying at least 20 subjects per sex and per decade between the ages of 20 and 80 years.With respect to the Global Lung Function Initiative reference data, our subjects had average z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC of -0.12, 0.04 and -0.32, respectively. Reference equations were obtained which could account for a potential dependence of index variability on age and height. This was done for (but not limited to) indices that are pertinent to asthma and chronic obstructive pulmonary disease studies: forced expired volume in 6 s, forced expiratory flow, TLCO, specific airway conductance, residual volume (RV)/total lung capacity (TLC), and ventilation heterogeneity in acinar and conductive lung zones.Deterioration in acinar ventilation heterogeneity and lung clearance index with age were more marked beyond 60 years, and conductive ventilation heterogeneity showed the greatest increase in variability with age. The most clinically relevant deviation from published reference values concerned RV/TLC values, which were considerably smaller than American Thoracic Society/European Respiratory Society-endorsed reference values.