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.

Collaboration between explainable artificial intelligence and pulmonologists improves the accuracy of pulmonary function test interpretation.

BACKGROUND: Few studies have investigated the collaborative potential between artificial intelligence (AI) and pulmonologists for diagnosing pulmonary disease. We hypothesised that the collaboration between a pulmonologist and AI with explanations (explainable AI (XAI)) is superior in diagnostic interpretation of pulmonary function tests (PFTs) than the pulmonologist without support. METHODS: The study was conducted in two phases, a monocentre study (phase 1) and a multicentre intervention study (phase 2). Each phase utilised two different sets of 24 PFT reports of patients with a clinically validated gold standard diagnosis. Each PFT was interpreted without (control) and with XAI's suggestions (intervention). Pulmonologists provided a differential diagnosis consisting of a preferential diagnosis and optionally up to three additional diagnoses. The primary end-point compared accuracy of preferential and additional diagnoses between control and intervention. Secondary end-points were the number of diagnoses in differential diagnosis, diagnostic confidence and inter-rater agreement. We also analysed how XAI influenced pulmonologists' decisions. RESULTS: In phase 1 (n=16 pulmonologists), mean preferential and differential diagnostic accuracy significantly increased by 10.4% and 9.4%, respectively, between control and intervention (p<0.001). Improvements were somewhat lower but highly significant (p<0.0001) in phase 2 (5.4% and 8.7%, respectively; n=62 pulmonologists). In both phases, the number of diagnoses in the differential diagnosis did not reduce, but diagnostic confidence and inter-rater agreement significantly increased during intervention. Pulmonologists updated their decisions with XAI's feedback and consistently improved their baseline performance if AI provided correct predictions. CONCLUSION: A collaboration between a pulmonologist and XAI is better at interpreting PFTs than individual pulmonologists reading without XAI support or XAI alone.

Therapeutical strategies in cavitary legionnaires' disease, two cases from the field and a systematic review.

BACKGROUND: Legionnaires' Disease (LD) rarely evolves into pulmonary abscesses. The current systematic review has been designed to explore therapeutical strategies in pulmonary cavitary LD. METHODS: A research strategy was developed and applied to the databases Embase, Pubmed, and Web of Science from the 1st of January 2000 to the 1st of November 2022. Original articles, case series, case reports, and guidelines written in English, French, German, Italian, and Dutch were considered. Furthermore, medical records of patients treated at the University Hospital UZ Brussel for LD cavitary pneumonia, between the 1st of January 2016 to the 1st of January 2022, were reviewed. RESULTS: Two patients were found by the UZ Brussel's medical records investigation. Through the literature review, 23 reports describing 29 patients, and seven guidelines were identified. The overall evidence level was low. RESULT OF SYNTHESIS (CASE REPORTS): The median age was 48 years and 65% were male. A polymicrobial infection was detected in 11 patients (44%) with other aerobic bacteria being the most commonly found. At diagnosis, 52% of patients received combination therapy, and fluoroquinolones were the preferred antimicrobial class. Anaerobic coverage was neglected in 33% of patients. RESULT OF SYNTHESIS (GUIDELINES): Three guidelines favor monotherapy with fluoroquinolones or macrolides, while one suggested an antimicrobial combination in case of severe LD. Four guidelines recommended anaerobic coverage in case of lung abscesses. CONCLUSION: To date, the evidence supporting cavitary LD treatment is low. Monotherapy lowers toxicity and might be as effective as combination therapy. Finally, anaerobes should not be neglected.

Getting the Most out of Spirometry: A Tool to Guide Dry Powder Inhaler Use.

BACKGROUND: Dry powder inhaler (DPI) use requires sufficient peak inspiratory flow over the DPI internal resistance (PIFR). OBJECTIVES: We examined whether spirometric peak inspiratory flow (PIFspiro) could serve to predict PIFR in patients with obstructive lung disease. METHOD: Thirty healthy nonsmokers and 140 stable outpatients (70 COPD, 70 asthma) performed spirometry according to the 2019 ERS/ATS spirometry update, yielding PIFspiro. Using a PIFR measurement device with varying orifices, all subjects' PIFR values were recorded for 5 predefined resistance levels, characterized by 5 orifice cross sections (SR). A test group including all healthy subjects, 30 of the asthma, and 30 of the COPD patients was used to establish the relationship between PIFR and both PIFspiro and SR by multiple regression. A validation group including the remaining 40 asthma and 40 COPD patients, served to verify whether their predicted PIFR value corresponded to the measured PIFR for each resistance level. RESULTS: The asthma (FEV1 = 78 ± 17 [SD] %pred) and COPD (FEV1 = 46 ± 17 [SD] %pred) patients under study had varying airway obstruction. In the test group, PIFR could be predicted by ln[PIFspiro] (p < 0.0001), SR (p < 0.0001), and SR2 (p = 0.006), with an adjusted R2 = 0.71. In the validation group, estimated PIFR did not significantly differ from measured PIFR (p > 0.05 for the 5 resistance levels). CONCLUSIONS: We propose a simple method to predict PIFR for a range of common DPI resistances, based on the device characteristics and on the patient's characteristics reflected in PIFspiro. As such, routine spirometry can serve to estimate a patient's specific PIFR without the need for additional testing.

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.

The stability of blood eosinophils in stable chronic obstructive pulmonary disease: a retrospective study in Belgian primary care.

BACKGROUND: Blood eosinophil counts (BEC) were recently included in the 2019 Global Initiative for Obstructive Lung Disease (GOLD) guideline as an easily accessible theragnostic biomarker for Chronic Obstructive Pulmonary Disease (COPD). However, the stability of BEC remains insufficiently studied. METHODS: We conducted a retrospective study in six primary care practices in Belgium on data from Electronic Health Records of stable COPD patients, to characterise the stability of blood eosinophils over time. We report the percentage of patients with BEC persistently below or above the 2019 GOLD guideline thresholds (100 and 300 cells/µL). For each patient the mean, standard deviation (SD) and relative standard deviation (RSD) of the BEC were calculated to determine the intra-patient variability. RESULTS: Ninety-eight patients were included, yielding 1082 eosinophil measurements (median 8 measurements/patient), with BEC ranging between 0 and 1504 cells/µL. Four (4.1%) patients had BEC persistently below 100 cells/µL, 34 (34.7%) had measurements persistently above this threshold. Approximately half of the patients (51.0%) had BEC persistently below 300 cells/µL and 3 (3.1%) patients had counts persistently above this threshold. 28.6% of patients crossed both threshold values throughout the registration period. The mean BEC per patient ranged between 15 and 846 cells/µL with an intra-patient SD between 5 and 658 cells/µL. The mean intra-patient RSD was 0.46. There was a significant strong positive correlation (Pearson analyses) between the mean BEC and SD (r = 0.765; n = 98). Simple linear regression was used to further describe the influence of the mean eosinophil count on the SD (B = 0.500; 95%CI 0.415-0.586; n = 98; p < 0.001). CONCLUSION: BEC can be variable in individual COPD patients. Therefore, the use of a single measurement to guide therapeutic decisions remains debatable. Further prospective research remains necessary to validate the reproducibility of this biomarker.

Two CFTR mutations within codon 970 differently impact on the chloride channel functionality.

Pharmacological rescue of mutant cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) depends on the specific defect caused by different mutation classes. We asked whether a patient with the rare p.Gly970Asp (c.2909G>A) mutation could benefit from CFTR pharmacotherapy since a similar missense mutant p.Gly970Arg (c.2908G>C) was previously found to be sensitive to potentiators in vitro but not in vivo. By complementary DNA transfection, we found that both mutations are associated with defective CFTR function amenable to pharmacological treatment. However, analysis of messenger RNA (mRNA) from patient's cells revealed that c.2908G>C impairs RNA splicing whereas c.2909G>A does not perturb splicing and leads to the expected p.Gly970Asp mutation. In agreement with these results, nasal epithelial cells from the p.Gly970Asp patient showed significant improvement of CFTR function upon pharmacological treatment. Our results underline the importance of controlling the effect of CF mutation at the mRNA level to determine if the pharmacotherapy of CFTR basic defect is appropriate.

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.

Evidence of an acinar response following treatment for exacerbation in adult patients with cystic fibrosis.

BACKGROUND: Treating acute infectious exacerbations in cystic fibrosis (CF) patients with intravenous antibiotic therapy leads to variability in lung function and the ventilation distribution response. Part of the variable lung clearance index (LCI) response could be associated with the variable peripheral effects of intravenous antibiotic administration. OBJECTIVES: We explored to what extent the peripheral lung zones of CF patients could contribute to lung function improvements following treatment for infectious exacerbations. METHODS: Over a 1-year period, 15 adult CF patients admitted for acute exacerbations were recruited. Lung function and multiple breath washout (MBW) tests were performed on the day of admission and at discharge. From the MBW test, we obtained acinar and conductive indices of ventilation heterogeneity and LCI. RESULTS: The mean age (±SD) was 26 ± 5 years. Upon admission, the FEV1 was 54 ± 16% predicted and the LCI was 181 ± 26% predicted. After treatment, the average FEV1 increased to 61 ± 20% predicted (p < 0.001) and the LCI decreased to 173 ± 28% predicted (p = 0.042). The change in LCI was associated with a change in acinar (ρ = +0.54; p = 0.039) but not in conductive ventilation heterogeneity (p > 0.1). CONCLUSIONS: In CF patients in whom an improvement in LCI was obtained after treatment for an acute infectious exacerbation, this was paralleled by a decrease in acinar ventilation heterogeneity.