Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.

BACKGROUND: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient. METHODS: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering. RESULTS: Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category. CONCLUSIONS: Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

Development and validation of a pulmonary function test data extraction tool for the US department of veterans affairs electronic health record.

OBJECTIVE: Pulmonary function test (PFT) results are recorded variably across hospitals in the Department of Veterans Affairs (VA) electronic health record (EHR), using both unstructured and semi-structured notes. We developed and validated a hospital-specific code to extract pre-bronchodilator measures of obstruction (ratio of forced expiratory volume in one second [FEV1] to forced vital capacity [FVC]) and severity of obstruction (percent predicted of FEV1). RESULTS: Among 36 VA facilities with the most PFTs completed between 2018 and 2022 from a parent cohort of veterans receiving long-acting controller inhalers, 12 had a consistent syntactical convention or template for reporting PFT data in the EHR. Of the 42,718 PFTs identified from these 12 facilities, the hospital-specific text processing pipeline yielded 24,860 values for the FEV1:FVC ratio and 23,729 values for FEV1. A ratio of FEV1:FVC less than 0.7 was identified in 17,615 of 24,922 studies (70.7%); 8864 of 24,922 (35.6%) had a severe or very severe reduction in FEV1 (< 50% of the predicted value). Among 100 randomly selected PFT reports reviewed by two pulmonary physicians, the coding solution correctly identified the presence of obstruction in 99 out of 100 studies and the degree of obstruction in 96 out of 100 studies.

Analysis of Endocrine and Inflammatory Markers in Preserved Ratio Impaired Spirometry.

Chronic Obstructive Pulmonary Disease (COPD) is a disease of the lungs characterized by chronic airflow obstruction. Individuals with preserved ratio impaired spirometry (PRISm) may be at risk for developing COPD. This study aimed to characterize PRISm and COPD patients in terms of their immune response and endocrine profile to identify differences extending beyond lung function. The participants performed the clinical assessment, pulmonary function test, and blood collection to determine serum hormone levels and concentrations of cytokine. Differences were observed in the nutritional status, lung function, and comorbidity. There were no differences in IL-6, IL-8, IL-10, IL-12, and TNF levels between PRISm and COPD groups. Both PRISm and COPD patients have lower dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. Correlation analysis of PRISm and COPD patients revealed positive correlations between serum levels of DHEA-S and DHEA, with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), which negatively correlated with IL-8 levels. The results indicated that despite differences in lung function parameters, the PRISm and COPD groups exhibited similarities in endocrine profile alterations. This study represents the first attempt to link endocrine with immune markers and lung function in individuals with PRISm.

Acquired tracheomalacia due to SARS-CoV-2 pneumonia.

INTRODUCTION: Several studies mentioned parenchymal findings after SARS-CoV-2 pneumonia, but few studies have mentioned alterations in the airways. The aim of this study was to estimate the prevalence of tracheomalacia and to analyse the clinical characteristics in a cohort of patients with SARS-CoV-2. METHODS: The study population consisted of all patients with SARS-CoV-2 admitted a hospital serving a population of 500 000 inhabitants. Patients were visited between 2 and 6 months after hospital discharge. In this visit, all patients were subjected to an exhaustive clinical questionnaire and underwent clinical examination, pulmonary function tests and chest CT. RESULTS: From February 2020 to August 2021, 1920 patients were included in the cohort and tracheomalacia was observed in 15 (0.8%) on expiratory HRCT imaging. All patients with tracheomalacia also presented ground glass opacities in the CT scan and 12 patients had airway sequelae. CONCLUSIONS: Tracheomalacia is an exceptional sequela of SARS-CoV-2 survivors.

The Value of Ultrasound for Detecting and Following Subclinical Interstitial Lung Disease in Systemic Sclerosis.

BACKGROUND: Interstitial lung disease (ILD) is a complication in patients with systemic sclerosis (SSc). Accurate strategies to identify its presence in early phases are essential. We conducted the study aiming to determine the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to ascertain its potential in determining the disease progression. METHODS: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), auscultation, chest radiographs, and respiratory function tests (RFT) were performed. A rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. The patients were followed every 12 weeks for 48 weeks. RESULTS: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p = 0.0001). Anti-centromere antibodies (p = 0.005) and RSS (p = 0.004) showed an association with ILD. A positive correlation was demonstrated between the US and HRCT findings (p = 0.001). The sensitivity and specificity of US in detecting ILD were 91.2% and 88.6%, respectively. In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. CONCLUSIONS: US showed a high prevalence of subclinical ILD in SSc patients. It proved to be a valid, reliable, and feasible tool to detect ILD in SSc and to monitor disease progression.

The contribution of estimated dead space fraction to mortality prediction in patients with chronic obstructive pulmonary disease-a new proposal.

Background: Mortality due to chronic obstructive pulmonary disease (COPD) is increasing. However, dead space fractions at rest (VD/VTrest) and peak exercise (VD/VTpeak) and variables affecting survival have not been evaluated. This study aimed to investigate these issues. Methods: This retrospective observational cohort study was conducted from 2010-2020. Patients with COPD who smoked, met the Global Initiatives for Chronic Lung Diseases (GOLD) criteria, had available demographic, complete lung function test (CLFT), medication, acute exacerbation of COPD (AECOPD), Charlson Comorbidity Index, and survival data were enrolled. VD/VTrest and VD/VTpeak were estimated (estVD/VTrest and estVD/VTpeak). Univariate and multivariable Cox regression with stepwise variable selection were performed to estimate hazard ratios of all-cause mortality. Results: Overall, 14,910 patients with COPD were obtained from the hospital database, and 456 were analyzed after excluding those without CLFT or meeting the lung function criteria during the follow-up period (median (IQR) 597 (331-934.5) days). Of the 456 subjects, 81% had GOLD stages 2 and 3, highly elevated dead space fractions, mild air-trapping and diffusion impairment. The hospitalized AECOPD rate was 0.60 ± 2.84/person/year. Forty-eight subjects (10.5%) died, including 30 with advanced cancer. The incidence density of death was 6.03 per 100 person-years. The crude risk factors for mortality were elevated estVD/VTrest, estVD/VTpeak, ≥2 hospitalizations for AECOPD, advanced age, body mass index (BMI) <18.5 kg/m2, and cancer (hazard ratios (95% C.I.) from 1.03 [1.00-1.06] to 5.45 [3.04-9.79]). The protective factors were high peak expiratory flow%, adjusted diffusing capacity%, alveolar volume%, and BMI 24-26.9 kg/m2. In stepwise Cox regression analysis, after adjusting for all selected factors except cancer, estVD/VTrest and BMI <18.5 kg/m2 were risk factors, whereas BMI 24-26.9 kg/m2 was protective. Cancer was the main cause of all-cause mortality in this study; however, estVD/VTrest and BMI were independent prognostic factors for COPD after excluding cancer. Conclusions: The predictive formula for dead space fraction enables the estimation of VD/VTrest, and the mortality probability formula facilitates the estimation of COPD mortality. However, the clinical implications should be approached with caution until these formulas have been validated.

Effects of a pulmonary rehabilitation program on pulmonary function, exercise performance, and quality of life in patients with severe COVID-19.

BACKGROUND: Severe coronavirus 2019 disease (COVID-19) causes acute hypoxemic respiratory failure requiring invasive mechanical ventilation (IMV). Once these symptoms are resolved, patients can present systemic deterioration. OBJECTIVE: The two objectives of this study were as follows: to describe the results of a pulmonary rehabilitation program (PRP), which is divided into three groups with different numbers of sessions (12, 24, and 36), and to associate the variables of pulmonary function, exercise performance, and functionality with the number of sessions and functional improvement. DESIGN: Prospective, observational study. METHODS: PRP consisted of aerobic + strength + flexibility exercises under the supervision and individualized into 12, 24, or 36 sessions (12s, 24s, and 36s), depending on the evolution of each patient. At the beginning of the study and immediately after the intervention, forced vital capacity (FVC), maximal inspiratory pressure, 6-minute walk test (6MWT), sit-to-stand test (STS), maximal handgrip strength (HGS), Fatigue Assessment Scale, Post-COVID-19 Functional Status (PCFS), and health-related quality of life (HRQoL) were measured. RESULTS: The proposed PRP demonstrated a positive effect on pulmonary function, exercise performance, and HRQoL, regardless of the number of sessions. A higher score on the PCFS and more days on IMV were associated with the increased likelihood of needing more sessions, whereas more meters on the 6MWT in the initial evaluation was associated with a reduced likelihood of needing more sessions. Finally, more repetitions on the STS and less distance covered on the initial 6MWT were associated with a greater improvement in exercise performance evaluated with the 6MWT. CONCLUSION: Supervised and individualized PRP for patients with severe post-COVID-19 improves pulmonary function, exercise performance, functionality, and quality of life. Functionality, distance covered on the 6MWT, and the days on IMV are central to the scheduling of the number of sessions for these patients.

Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. METHODS: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. RESULTS: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. CONCLUSION: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

The dynamics of recovery of external breathing function in patients after laparoscopic cholecystectomy in the acute period under the influence of the rehabilitation program.

OBJECTIVE: Aim: To determine the dynamics of renewal of the function of external respiration in patients after laparoscopic cholecystectomy at the acute stage of rehabilitation under the influence of a rehabilitation program. PATIENTS AND METHODS: Materials and Methods: The study is randomized, simple with blinded assessors. The forced vital capacity (FVC, l), forced expiratory volume in the first second (FEV1, l) and peak expiratory flow rate (PEFR, l/s) were assessed. Spirometry was performed 120 patients on the first day of admission of patients to the surgical department for surgical intervention, on the second day and on the day of discharge. Methods of mathematical statistics: arithmetic mean (M) and standard error of the mean (}m), Student's t-test were calculated, differences at p<0,05 were considered statistically significant. RESULTS: Results: It has been established that laparoscopic cholecystectomy leads to a statistically significant decrease in the parameters of respiratory function in all age categories. More pronounced positive dynamics of respiratory function in the group of respiratory therapy. It was established that without respiratory therapy on the day of discharge there was no restoration (р<0.05) in groups of elderly patients of group of FVC l, FEV1 l, PEFR l/s; in middle-aged patients did no restoration FEV1, l, PEFR, l/s; in younger patients there was no recovery of FEV1, l. CONCLUSION: Conclusions: The results of the study indicate the effectiveness of the introduction of diaphragmatic breathing exercises in combination with early mobilization at the acute and subacute stages of rehabilitation in patients after laparoscopic cholecystectomy in order to restore the function of the respiratory system.

The effect of craniocervical flexion and neck endurance exercises plus pulmonary rehabilitation on pulmonary function in spinal cord injury: a pilot single-blinded randomised controlled trial.

STUDY DESIGN: Randomised controlled trial with computerised allocation, assessor blinding and intention-to-treat analysis. OBJECTIVE: This study wanted to prove that cervicocranial flexion exercise (CCFE) and superficial neck flexor endurance training combined with common pulmonary rehabilitation is feasible for improving spinal cord injury people's pulmonary function. SETTING: Taoyuan General Hospital, Ministry of Health and Welfare: Department of Physiotherapy, Taiwan. METHOD: Thirteen individuals who had sustained spinal cord injury for less than a year were recruited and randomised assigned into two groups. The experimental group was assigned CCFEs and neck flexor endurance training plus normal cardiopulmonary rehabilitation. The control group was assigned general neck stretching exercises plus cardiopulmonary rehabilitation. Lung function parameters such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow rate (PEFR), inspiratory capacity (IC), dyspnoea, pain, and neck stiffness were recorded once a week as short-term outcome measure. RESULT: The experimental group showed significant time effects for FVC (pre-therapy: 80.4 ± 21.4, post-therapy: 86.9 ± 16.9, p = 0.021, 95% CI: 0.00-0.26) and PEFR (pre-therapy: 67.0 ± 33.4; post-therapy: 78.4 ± 26.9, p = 0.042, 95% CI: 0.00-0.22) after the therapy course. Furthermore, the experimental group showed significant time effects for BDI (experimental group: 6.3 ± 3.0; control group: 10.8 ± 1.6, p = 0.012, 95% CI: 0.00-0.21). CONCLUSION: The exercise regime for the experimental group could efficiently increase lung function due to the following three reasons: first, respiratory accessory muscle endurance increases through training. Second, posture becomes less kyphosis resulting increasing lung volume. Third, the ratio between superficial and deep neck flexor is more synchronised. IRB TRIAL REGISTRATION: TYGH108045. CLINICAL TRIAL REGISTRATION: NCT04500223.

Predicting parameters of airway dynamics generated from inspiratory and expiratory plethysmographic airway loops, differentiating subtypes of chronic obstructive diseases.

BACKGROUND: The plethysmographic shift volume-flow loop (sRaw-loop) measured during tidal breathing allows the determination of several lung function parameters such as the effective specific airway resistance (sReff), calculated from the ratio of the integral of the resistive aerodynamic specific work of breathing (sWOB) and the integral of the corresponding flow-volume loop. However, computing the inspiratory and expiratory areas of the sRaw-loop separately permits the determination of further parameters of airway dynamics. Therefore, we aimed to define the discriminating diagnostic power of the inspiratory and expiratory sWOB (sWOBin, sWOBex), as well as of the inspiratory and expiratory sReff (sReff IN and sReff EX), for discriminating different functional phenotypes of chronic obstructive lung diseases. METHODS: Reference equations were obtained from measurement of different databases, incorporating 194 healthy subjects (35 children and 159 adults), and applied to a collective of 294 patients with chronic lung diseases (16 children with asthma, aged 6-16 years, and 278 adults, aged 17-92 years). For all measurements, the same type of plethysmograph was used (Jaeger Würzburg, Germany). RESULTS: By multilinear modelling, reference equations of sWOBin, sWOBex, sReff IN and sReff EX were derived. Apart from anthropometric indices, additional parameters such as tidal volume (VT), the respiratory drive (P0.1), measured by means of a mouth occlusion pressure measurement 100 ms after inspiration and the mean inspiratory flow (VT/TI) were found to be informative. The statistical approach to define reference equations for parameters of airway dynamics reveals the interrelationship between covariants of the actual breathing pattern and the control of breathing. CONCLUSIONS: We discovered that sWOBin, sWOBex, sReff IN and sReff EX are new discriminating target parameters, that differentiate much better between chronic obstructive diseases and their subtypes, especially between chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO), thus strengthening the concept of precision medicine.

Influence of acclimatization time on parameters of barometric whole-body plethysmography in healthy adult cats.

BACKGROUND: Pulmonary function testing by barometric whole-body plethysmography (BWBP) is a long-established and well-accepted, non-invasive investigative procedure in cats. HYPOTHESIS/OBJECTIVES: To evaluate, if different acclimatization times influence the measurement parameters of BWBP in healthy adult cats. ANIMALS: 48 healthy adult cats. METHODS: In the prospective observational study, healthy cats were placed in a measuring chamber and BWBP was performed over 30 minutes. Parameters obtained during the three measurement units of 10 minutes each (T1, T2 and T3) were compared. RESULTS: All measurement parameters except for tidal volume per body weight changed significantly (p<0.05) over the three time periods. From T1-T2, the parameters minute volume per body weight (p<0.001), peak inspiratory flow per body weight (p<0.001), peak expiratory flow per body weight (p = 0.002), pause (p = 0.03), enhanced pause (p = 0.03) and quotient of peak expiratory flow divided by expiratory flow at end expiratory volume plus 50% tidal volume (p = 0.03) changed significantly. From the time interval T2-T3, only respiratory rate (p = 0.02), inspiratory time (p = 0.02), expiratory time (p = 0.04), and relaxation time (p = 0.01) changed significantly. All measurement parameters except for tidal volume per body weight changed significantly (p<0.05) between T1 and T3. Age had a significant influence on all parameters except for peak expiratory flow per body weight and peak inspiratory flow per body weight. The parameters were not influenced by sex. CONCLUSION AND CLINICAL IMPORTANCE: All measurement parameters except tidal volume per body weight were significantly affected by acclimatization time. Controlling for age and sex, there was still a significant influence of acclimatization time on all parameters except for tidal volume per body weight. Standardization of the acclimatization time for future studies would be appropriate in order to maintain comparability.

FEV1Q: a race-neutral approach to assessing lung function.

BACKGROUND: Forced expiratory volume in 1 s quotient (FEV1Q) is a simple approach to spirometry interpretation that compares measured lung function to a lower boundary. This study evaluated how well FEV1Q predicts survival compared with current interpretation methods and whether race impacts FEV1Q. METHODS: White and Black adults with complete spirometry and mortality data from the National Health and Nutrition Examination Survey (NHANES) III and the United Network for Organ Sharing (UNOS) database for lung transplant referrals were included. FEV1Q was calculated as FEV1 divided by 0.4 L for females or 0.5 L for males. Cumulative distributions of FEV1 were compared across races. Cox proportional hazards models tested mortality risk from FEV1Q adjusting for age, sex, height, smoking, income and among UNOS individuals, referral diagnosis. Harrell's C-statistics were compared between absolute FEV1, FEV1Q, FEV1/height2, FEV1 z-scores and FEV1 % predicted. Analyses were stratified by race. RESULTS: Among 7182 individuals from NHANES III and 7149 from UNOS, 1907 (27%) and 991 (14%), respectively, were Black. The lower boundary FEV1 values did not differ between Black and White individuals in either population (FEV1 first percentile difference ≤0.01 L; p>0.05). Decreasing FEV1Q was associated with increasing hazard ratio (HR) for mortality (NHANES III HR 1.33 (95% CI 1.28-1.39) and UNOS HR 1.18 (95% CI 1.12-1.23)). The associations were not confounded nor modified by race. Discriminative power was highest for FEV1Q compared with alternative FEV1 approaches in both Black and White individuals. CONCLUSIONS: FEV1Q is an intuitive and simple race-neutral approach to interpreting FEV1 that predicts survival better than current alternative methods.

The effect of electromyography triggered electrical stimulation to abdominal muscles on sitting balance, respiratory functions, and abdominal muscle thickness in complete spinal cord injury: a randomized controlled trial.

Complete thoracic spinal cord injury (SCI) results in a loss of innervation to the abdominal muscles, which affects trunk stability and performance of activities of daily living from a sitting position. Respiratory function is also affected, leading to frequent pulmonary complications. Given the importance of trunk stability and respiratory function, we investigated the effects of electromyography triggered electrical stimulation (EMG-ES) applied to the abdominal muscles on sitting balance, respiratory functions and abdominal muscle thickness in individuals with complete thoracic SCI. This randomized controlled study included 34 participants with complete thoracic SCI who were randomly allocated to the experimental group ( n  = 17) and the control group ( n  = 17). During the 4-week intervention period, the experimental group received EMG-ES to their abdominal muscles, while the control group received isometric abdominal exercises three times per week. Both groups continued with their routine rehabilitation program (active or passive range of motion exercises, stretching, and balance coordination exercises). The primary outcome measures were the modified functional reach test (mFRT) and trunk control test (TCT). Secondary outcome measures included a pulmonary function test (PFT) and the bilateral abdominal muscle thicknesses using ultrasonography. At the end of the study, the experimental group showed significantly greater improvements in both primary outcomes. The mean difference in pre-post changes between the groups for the mFRT area was 242.8 cm² [95% confidence interval (CI): 181.3-329.8; effect size 0.92; P  < 0.001] and 5.0 points for TCT (95% CI: 3.9-6.0; effect size 0.98, P  < 0.001). The increase in the abdominal muscle thickness was also significantly greater in the experimental group ( P  < 0.001) without significant differences in the PFT ( P  > 0.05). We conclude that adding EMG-ES of abdominal muscles may further improve sitting balance and abdominal muscle thickness in individuals with complete thoracic SCI.

Using the gli spirographic prediction equations to revisit the allometric relationships between lung volumes, height and age in adults.

The determination the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) during spirometry studies, is at the core of the evaluation of the pulmonary function of patients with respiratory diseases. The Global Lung Function Initiative (GLI) offers the most extensive data set of normal lung functions available, which is currently used to determine the average expected/predicted FEV1 and FVC (predV), and their lower limit of normal (LLN, 5th percentile) at any given height and age for women and men. These prediction equations are currently expressed in a rather complex form: predV = exp [p+ (a x Ln (height) + (n x Ln (age)) + spline] and LLN = exp(Ln (predV) + Ln (1 - 1.645 x S x CV)/S); and are currently used to generate interpretations in commercialized spinographic system. However, as shown in this paper, these equations contain physiological and fundamental allometric information on lung volumes that become obvious when rewriting mean predicted values as a "simple" power function of height and LLN as a percentage of the mean predicted values. We therefore propose to present the equations of prediction obtained from the GLI data using simplified expressions in adults (18-95 years old) to reveal some of their physiological and allometric meaning. Indeed, when predicted FEV1 and FVC (predV) were expressed under the form predV= αx heightax b(age), the resulting exponent (a) ranges between 2 and 3, transforming the one dimension of a length (size) into a volume, akin to the third-order power (cubic) function of height historically used to predict lung volumes. Only one function, b (age), is necessary to replace all the factors related to age, including the tables of discrete data of spline functions original equations. Similarly, LLN can be expressed as LLN = c (age) xpredV to become a simple percentage of the predicted values, as a function of age. The equations with their respective new polynomial functions were validated in 52,764 consecutive spirometry tests performed in 2022 in 22,612 men and 30,152 women at the Cleveland Clinic. Using these equations, it become obvious that for both women and men, FEV1/FVC ratio decreases with the size as the exponent of the power function of height is lower for FEV1 than FVC. We conclude that rewriting the GLI predicted equations with simpler formulations restitutes to the GLI data some of their original allometric meaning, without altering the accuracy of their prediction.

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.

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study.

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Cardiopulmonary exercise testing on adaptive equipment in children and adults with Friedreich ataxia.

INTRODUCTION/AIMS: Traditional exercise is often difficult for individuals with Friedreich ataxia (FRDA), and evidence is limited regarding how to measure exercise performance in this population. We evaluated the feasibility, reliability, and natural history of adaptive cardiopulmonary exercise test (CPET) performance in children and adults with FRDA. METHODS: Participants underwent CPET on either an arm cycle ergometer (ACE) or recumbent leg cycle ergometer (RLCE) at up to four visits (baseline, 2 weeks, 4 weeks, and 1 year). Maximum work, oxygen consumption (peak VO2), oxygen (O2) pulse, and anaerobic threshold (AT) were measured in those who reached maximal volition. Test-retest reliability was assessed with intraclass coefficients, and longitudinal change was assessed using regression analysis. RESULTS: In our cohort (N = 23), median age was 18 years (interquartile range [IQR], 14-23), median age of FRDA onset was 8 years (IQR 6-13), median Friedreich Ataxia Rating Scale score was 58 (IQR 54-62), and GAA repeat length on the shorter FXN allele (GAA1) was 766 (IQR, 650-900). Twenty-one (91%) completed a maximal CPET (n = 8, ACE and n = 13, RLCE). Age, sex, and GAA1 repeat length were each associated with peak VO2. Preliminary estimates demonstrated reasonable agreement between visits 2 and 3 for peak work by both ACE and RLCE, and for peak VO2, O2 pulse, and AT by RLCE. We did not detect significant performance changes over 1 year. DISCUSSION: Adaptive CPET is feasible in FRDA, a relevant clinical trial outcome for interventions that impact exercise performance and will increase access to participation as well as generalizability of findings.