Updated reference values for static lung volumes from a healthy population in Austria.

BACKGROUND: Reference values for lung volumes are necessary to identify and diagnose restrictive lung diseases and hyperinflation, but the values have to be validated in the relevant population. Our aim was to investigate the Global Lung Function Initiative (GLI) reference equations in a representative healthy Austrian population and create population-derived reference equations if poor fit was observed. METHODS: We analysed spirometry and body plethysmography data from 5371 respiratory healthy subjects (6-80 years) from the Austrian LEAD Study. Fit with the GLI equations was examined using z-scores and distributions within the limits of normality. LEAD reference equations were then created using the LMS method and the generalized additive model of location shape and scale package according to GLI models. RESULTS: Good fit, defined as mean z-scores between + 0.5 and -0.5,was not observed for the GLI static lung volume equations, with mean z-scores > 0.5 for residual volume (RV), RV/TLC (total lung capacity) and TLC in both sexes, and for expiratory reserve volume (ERV) and inspiratory capacity in females. Distribution within the limits of normality were shifted to the upper limit except for ERV. Population-derived reference equations from the LEAD cohort showed superior fit for lung volumes and provided reproducible results. CONCLUSION: GLI lung volume reference equations demonstrated a poor fit for our cohort, especially in females. Therefore a new set of Austrian reference equations for static lung volumes was developed, that can be applied to both children and adults (6-80 years of age).

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.

Effects of mixed hardwoods dust on respiratory function and blood immunoglobulin levels in wood workers.

Background: Occupational exposure to wood dust, generated by various individual wood species, both softwood and hardwood, has been extensively documented as a causative factor for reduced lung function, frequent respiratory symptoms, and increased immunological responses in wood workers. This study explores the impact of wood dust from mixed tropical hardwood species on lung function, respiratory symptoms, and Immunoglobulin (Ig) E and G levels. Methods: A cross-sectional study was conducted among wood workers at the Accra Timber Market and a control group from the University of Ghana. Particulate matter (PM) was sampled using a Minivol Sampler set to a flow rate of 5 l/min. Respiratory symptoms were assessed using questions adapted from the British Medical Research Council (MRC) questionnaire (1960). Lung volumes and airflow rates were measured using a spirometer. Total serum IgE and IgG levels were quantified using ELISA. Results: No significant differences were observed between the wood workers and the controls for demographic variables. Wood workers exhibited a significantly higher prevalence of respiratory symptoms, particularly rhinitis, with many reporting the absence of symptoms during holidays. Lung function parameters (VC, FEV1, FEV1%, PEFR, and FEF25-75%) were significantly reduced (p < 0.05) in wood workers. A significant negative correlation was noted between lung function parameters and years of exposure to wood dust. Wood workers showed significantly elevated levels (p < 0.05) of IgG and IgE. Conclusion: The study findings suggest that exposure to mixed tropical hardwood dust induces elevated blood IgE and IgG levels, along with non-allergic respiratory function abnormalities.

Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-COPD? A Prospective, Population-based Cohort Study.

RATIONALE: The term 'pre-COPD' refers to individuals at high-risk of developing Chronic Obstructive Pulmonary Disease (COPD) who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. OBJECTIVE: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at-risk of developing COPD. METHODS: The Tasmanian Longitudinal Health Study is a population-based cohort first studied in 1968 (age 7). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity and static lung volumes were measured on a subgroup at age 45, and incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden Index. MEASUREMENTS AND MAIN RESULTS: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score < -1.264, corresponding to the lowest 10th percentile. Those below this threshold had 36-fold increased risk of developing COPD over an eight-year follow-up period (RR 35.8, 95%CI 8.88 to 144), corresponding to a risk difference of +16.4% (95%CI 3.7-67.4). The sensitivity was 88% and specificity 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. CONCLUSION: Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high-risk of developing COPD in community-based settings.

Effects of Weight Change and Weight Cycling on Lung Function in Overweight and Obese Adults.

Rationale: Epidemiological studies have reported on the detrimental effects on lung function after natural, and thus limited, weight gain in unselected populations. Studies on bariatric surgery, on the contrary, have indicated large improvements in lung function after substantial weight loss. Objectives: To study the associations between profound weight loss or gain and pulmonary function within the same population. A second objective was to investigate the effect of weight cycling on pulmonary function. Methods: From our lung function database, we selected the records of subjects in follow-up for continuous positive airway pressure therapy for sleep apnea with a weight change of ⩾20 kg within 5 years. Lung function (N = 255) at baseline was normal except for a tendency toward mild restriction in morbid obesity. Within this sample, 73 subjects were identified with significant "weight cycling", defined as a ⩾10-kg opposite change in body weight before or after the ⩾20-kg weight change. Results: Weight change affected pulmonary function more in men than in women (P < 0.001). In men, forced vital capacity (FVC) increased an average of 1.4% predicted per unit of body mass index after weight loss and the reverse after weight gain, whereas women exhibited a smaller change of 0.9% predicted per unit of body mass index. Weight loss slightly increased the ratio of forced expiratory volume in 1 second to FVC and decreased the specific airway resistance, whereas the opposite occurred with weight gain. Greater effects of weight change on lung function were observed in leaner subjects (P = 0.02) and in older subjects (P < 0.002). Changes in total lung capacity followed the changes in FVC, with no change in residual volume, and the greatest change was observed in functional residual capacity. In subjects with weight cycling, the improvement in lung function due to weight loss was reversed by subsequent weight gain and vice versa. Conclusions: This study provides evidence that the detrimental effect of obesity on lung function is a passive and reversible process.

Enhancing respiratory physiology education: innovative wet spirometer modifications for hands-on learning.

The use of wet spirometers, although once common, has greatly declined because these devices measure only static lung volumes and students often face technical issues in their use. In this study, the wet spirometer has been modified to investigate the fundamental laws of flow and different types of lung disease. This modification was achieved by changing the dimensions of the device, printing a scale on the bell, and attaching an airflow control system (ACS) between the corrugated tube and hollow tube of the inner cylinder. The ACS allowed for flow control during the exercises. Two exercises were performed: exercise I compared the parameters measured by the wet spirometer, modified spirometer, and computerized spirometer to determine the suitability of the modification, while exercise II tested the variables affecting flow. These exercises introduce students to data collection, analysis, and the use of statistical tests as they compare various spirometers. Additionally, students gain valuable experience in experimental design by conducting diverse experiments that investigate factors influencing flow dynamics. By plotting the results and participating in small group discussions, students can apply flow principles in respiratory and circulatory systems, offering a hands-on experience that integrates physics and physiology. The modified spirometer facilitated multifaceted topic exploration, surpassing the traditional wet spirometer's capabilities.NEW & NOTEWORTHY This activity involves cost-effective modifications to the wet spirometer, broadening its applicability. These modifications effectively address student challenges associated with wet spirometer handling and enhance comprehension of fluid dynamics, all without the need for costly simulations, wet experiments, or fragile instruments. By offering a hands-on experience without traditional limitations, our modified spirometer provides an accessible and engaging approach to respiratory physiology education.

Ventilatory limitations in patients with HFpEF and obesity.

Heart failure with preserved ejection fraction (HFpEF) patients have an increased ventilatory demand. Whether their ventilatory capacity can meet this increased demand is unknown, especially in those with obesity. Body composition (DXA) and pulmonary function were measured in 20 patients with HFpEF (69 ± 6 yr;9 M/11 W). Cardiorespiratory responses, breathing mechanics, and ratings of perceived breathlessness (RPB, 0-10) were measured at rest, 20 W, and peak exercise. FVC correlated with %body fat (R2 =0.51,P = 0.0006), V̇O2peak (%predicted,R2 =0.32,P = 0.001), and RPB (R2 =0.58,P = 0.0004). %Body fat correlated with end-expiratory lung volume at rest (R2 =0.76,P < 0.001), 20 W (R2 =0.72,P < 0.001), and peak exercise (R2 =0.74,P < 0.001). Patients were then divided into two groups: those with lower ventilatory reserve (FVC<3 L,2 M/10 W) and those with higher ventilatory reserve (FVC>3.8 L,7 M/1 W). V̇O2peak was ∼22% less (p < 0.05) and RPB was twice as high at 20 W (p < 0.01) in patients with lower ventilatory reserve. Ventilatory reserves are limited in patients with HFpEF and obesity; indeed, the margin between ventilatory demand and capacity is so narrow that exercise capacity could be ventilatory limited in many patients.

Changes in Lung Volumes with Spirometric Disease Progression in COPD.

Background: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear. Methods: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.S. Department of Veterans Affairs electronic health records (n=71,356) and lung volumes measured by computed tomography (supine posture) available from the COPD Genetic Epidemiology (COPDGene®) study (n=7969) and the SubPopulations and InterMediate Outcome Measures In COPD Study (SPIROMICS) (n=2552) cohorts, and studied their cross-sectional distributions and longitudinal changes across the airflow obstruction spectrum. Patients with preserved ratio-impaired spirometry (PRISm) were excluded from this analysis. Results: Lung volumes from all 3 cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction. The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases. When stratified by airflow obstruction using Global initiative for chronic Obstructive Lung Disease (GOLD) stages, patients with GOLD 1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD 0 (smokers with preserved spirometry) or GOLD 2 (moderate) disease. In longitudinal follow-up of baseline GOLD 0 patients who progressed to spirometric COPD, those with an initially higher TLC and VC developed mild obstruction (GOLD 1) while those with an initially lower TLC and VC developed moderate obstruction (GOLD 2). Conclusions: In COPD, TLC, and VC have biphasic distributions, change in nonlinear fashions as obstruction worsens, and could differentiate those GOLD 0 patients at risk for more rapid spirometric disease progression.

Quantitative Assessment of Lung Volumes and Enhancement in Patients with COVID-19: Role of Dual-Energy CT.

Dual-energy computed tomography (DECT) has been used for detecting pulmonary embolism, but the role of lung perfusion DECT as a predictor of prognosis of coronavirus disease 2019 (COVID-19) has not been defined yet. The aim of our study was to explore whether the enhancement pattern in COVID-19+ patients relates to the disease outcome. A secondary aim was to compare the lung volumes in two subgroups of patients. In this observational study, we considered all consecutive COVID-19+ patients who presented to the emergency room between January 2021 and December 2021 with respiratory symptoms (with mild to absent lung consolidation) and were studied by chest contrast-enhanced DECT to be eligible. Two experienced radiologists post-processed the images using the "lung-analysis" software (SyngoVia). Absolute and relative enhancement lung volumes were assessed. Patients were stratified in two subgroups depending on clinical outcome at 30 days: (i) good outcome (i.e., discharge, absence of clinical or imaging signs of disease); (ii) bad outcome (i.e., hospitalization, death). Patient sub-groups were compared using chi-square test or Fisher test for qualitative parameters, chi-square test or Spearman's Rho test for quantitative parameters, Students' t-test for parametric variables and Wilcoxon test for non-parametric variables. We enrolled 78 patients (45M), of whom, 16.7% had good outcomes. We did not observe any significant differences between the two groups, both in terms of the total enhancement evaluation (p = 0.679) and of the relative enhancement (p = 0.918). In contrast, the average lung volume of good outcome patients (mean value of 4262 mL) was significantly larger than that of bad outcome patients (mean value of 3577.8 mL), p = 0.0116. All COVID-19+ patients, with either good or bad outcomes, presented similar enhancement parameters and relative enhancements, underlining no differences in lung perfusion. Conversely, a significant drop in lung volume was identified in the bad outcome subgroup eligible compared to the good outcome subgroup.

Abnormalities in pulmonary function and volumes in patients with CHD: a systematic review.

BACKGROUND: Lung function and cardiac function are naturally correlated by sharing the thoracic cage and handling the whole cardiac output sequentially. However, lung function studies are rare in patients with CHD, although results worthy of investigation could be expected. This review summarises existing studies with the lung function parameters (spirometry and body plethysmography) in CHD patients during the last decade. METHODS: A systematic review was performed in the relevant database (PubMed, Cochrane, and Scopus) in studies including paediatric and adult patients with CHD where lung parameters (spirometry, body plethysmography) were investigated from January 2010 to December 2020. Two independent reviewers evaluated the studies according to the Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung, and Blood Institute. RESULTS: Eight studies investigated patients with Fontan palliation including 704 patients (306 female). Four studies included patients after repaired tetralogy of Fallot examining 219 patients (103 female), with one study using double. Further six studies included 3208 (1324 female) children and adults with various CHDs. Overall, four studies were categorised as "good", ten as "fair", and four as "poor". While the measurements were consistently standardised, references to calculate %predicted differed substantially across all studies. All evaluated studies showed reduced forced vital capacity in the majority of CHD patients. CONCLUSIONS: Many CHD patients have a reduced forced vital capacity independent of their underlying defect. Spirometry should not only follow a standardised measure according to ATS (update 2019) but also stick to the 2012 GLI reference values.

Single Breath Counting for Diagnosis and Prediction of Severity of Acute Asthma Exacerbation in Children.

OBJECTIVES: To find correlation between single breath counting (SBC) and spirometry in acute exacerbation of asthma in children. METHODS: A cross-sectional observational study including all children aged 6-12 y age, who presented in outpatient department or emergency room with acute exacerbation of asthma, not fitting in exclusion criteria were enrolled. SBC and spirometry parameters were obtained before treatment and 1 h after initiating treatment (GINA 2017 Guidelines). RESULTS: Significant correlation was observed in SBC and FVC (r = 0.349), FEV1 (r = 0.439), FEF25-75 (r = 0.424), and PEF (r = 0.593). Cutoff value of SBC of 23 was found to be suggestive of severe/life-threatening asthma with sensitivity of 83.3% and specificity of 84.4%. No significant association was found between percent change in SBC and spirometry parameters in response to treatment. CONCLUSIONS: SBC can be used to predict PEF, FEV1, FVC, and FEF25-75 of a patient aged between 6 and 12 y during acute asthma exacerbation. The observed cutoff value of 23 of SBC score has a good sensitivity and specificity to identify life-threatening/severe exacerbation. SBC score significantly increases in response to therapy.

Higher Work of Breathing During Exercise in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: It is unknown if pulmonary alterations in heart failure with preserved ejection fraction (HFpEF) impact respiratory mechanics during exercise. RESEARCH QUESTION: Are the operating lung volumes, work of breathing (Wb), and power of breathing (Pb) abnormal in patients with HFpEF during exercise? STUDY DESIGN AND METHODS: Patients with HFpEF (n = 8; median age, 71 years [interquartile range (IQR), 66-80 years]) and control participants (n = 9; median age, 68 years [IQR, 64-74 years]) performed incremental cycling to volitional exhaustion. Esophageal pressure, end-expiratory lung volume (EELV), inspiratory lung volume (EILV), and ventilatory variables were compared at similar absolute (30 and 50 L/min) and relative (45% of peak, 70% of peak, and 100% of peak) minute ventilation (V.E) during exercise. RESULTS: During exercise, EELVs were not different between patients with HFpEF and control participants (P > .13 for all). EILVs were lower in patients with HFpEF than control participants at 45% and 70% V.E peak (P < .03 for all). Dynamic lung compliance was lower in patients with HFpEF than control participants at 30 L/min, 50 L/min, 45% V.E peak, and 100% V.E peak (P < .04 for all). Compared with control participants, patients with HFpEF showed higher total Wb and Pb at 30 L/min (Wb: median, 1.08 J/L [IQR, 0.93-1.82 J/L] vs 0.52 J/L [IQR, 0.43-0.71 J/L]; Pb: median, 36 J/min [IQR, 30-59 J/min] vs 17 J/min [IQR, 11-23 J/min] and 50 L/min; Wb: median, 1.40 J/L [IQR, 1.27-1.68 J/L] vs 0.90 J/L [IQR, 0.74-1.05 J/L]; Pb: median, 73 J/min [IQR, 60-83 J/min] vs 45 J/min [IQR, 33-63 J/min]; P < .01 for all). At 30 and 50 L/min, inspiratory and expiratory resistive Wb and Pb were higher in patients with HFpEF than control participants (P < .04 for all). Total Wb was higher for patients with HFpEF than control participants at 45% of V.E peak (P = .02). Total Pb was higher for control participants than patients with HFpEF at 100% V.E peak because of higher inspiratory resistive Pb (P < .04 for both). INTERPRETATION: These data demonstrate the HFpEF syndrome is associated with pulmonary alterations eliciting a greater Pb during exercise resulting from greater inspiratory and expiratory resistive Pb.

Lung-protective ventilation during Trendelenburg pneumoperitoneum surgery: A randomized clinical trial.

Study objective To assess the effects of a protective ventilation strategy during Trendelenburg pneumoperitoneum surgery on postoperative oxygenation. DESIGNS: Parallel-group, randomized trial. SETTING: Operating room of a university hospital, Italy. PATIENTS: Morbidly obese patients undergoing Trendelenburg pneumoperitoneum gynaecological surgery. INTERVENTIONS: Participants were randomized to standard (SV: tidal volume = 10 ml/kg of predicted body weight, PEEP = 5 cmH2O) or protective (PV: tidal volume = 6 ml/kg of predicted body weight, PEEP = 10 cmH2O, recruitment maneuvers) ventilation during anesthesia. MEASUREMENTS: Primary outcome was PaO2/FiO2 one hour after extubation. Secondary outcomes included day-1 PaO2/FiO2, day-2 respiratory function and intraoperative respiratory/lung mechanics, assessed through esophageal manometry, end-expiratory lung volume (EELV) measurement and pressure-volume curves. MAIN RESULTS: Sixty patients were analyzed (31 in SV group, 29 in PV group). Median [IqR] tidal volume was 350 ml [300-360] in PV group and 525 [500-575] in SV group. Median PaO2/FiO2 one hour after extubation was 280 mmHg [246-364] in PV group vs. 298 [250-343] in SV group (p = 0.64). Day-1 PaO2/FiO2, day-2 forced vital capacity, FEV-1 and Tiffenau Index were not different between groups (all p > 0.10). Intraoperatively, 59% of patients showed complete airway closure during pneumoperitoneum, without difference between groups: median airway opening pressure was 17 cmH2O. In PV group, airway and transpulmonary driving pressure were lower (12 ± 5 cmH2O vs. 17 ± 7, p < 0.001; 9 ± 4 vs. 13 ± 7, p < 0.001), PaCO2 and respiratory rate were higher (48 ± 8 mmHg vs. 42 ± 12, p < 0.001; 23 ± 5 breaths/min vs. 16 ± 4, p < 0.001). Intraoperative EELV was similar between PV and SV group (1193 ± 258 ml vs. 1207 ± 368, p = 0.80); ratio of tidal volume to EELV was lower in PV group (0.45 ± 0.12 vs. 0.32 ± 0.09, p < 0.001). CONCLUSIONS: In obese patients undergoing Trendelenburg pneumoperitoneum surgery, PV did not improve postoperative oxygenation nor day-2 respiratory function. PV was associated with intraoperative respiratory mechanics indicating less injurious ventilation. The high prevalence of complete airway closure may have affected study results. TRIAL REGISTRATION: Prospectively registered on http://clinicaltrials.govNCT03157479 on May 17th, 2017.

The Association of Self-Reported Birthweight with Lung Function and Respiratory Diseases: Results from a Multi-Centre, Multi-Case Control Study in Italy.

Early life conditions are associated with lung function and the development of respiratory and non-respiratory illnesses. The relationship with birthweight (BW), however, is conflicting. We examined associations of self-reported BW with lung function and the development of respiratory and also non-respiratory diseases within the GEIRD (Gene-Environment Interaction in Respiratory Diseases) project, an Italian multi-centre, multi-case control study involving cases of COPD, asthma, allergic rhinitis and controls. Multinomial logistic regression was performed with case/control status as response variable; BW as main determinant; and adjusting for sex, age and smoking status. Of the 2287 participants reporting BW, 6.4% (n = 147) had low BW (<2500 g), and this proportion was greater in women than men (7.8% vs. 5.1%; p = 0.006). Both men and women with low BW were shorter than those with normal BW (mean ± SD: 160.2 ± 5.5 vs. 162.6 ± 6.5 cm in women, p = 0.009; 172.4 ± 6.1 vs. 174.8 ± 7.2 cm in men, p < 0.001). Although FEV1 and FVC were reduced in individuals with low BW, this was explained by associations with sex and height. In multivariable analysis, BW was not associated with respiratory diseases in adulthood. However, those with low BW had a higher risk of self-reported hospitalisation for lung disease before the age of two (10.3% vs. 4.1%; p < 0.001), severe respiratory infection before the age of five (16.9% vs. 8.8%; p = 0.001) and hypertension in adulthood (29.9% vs. 23.7%; p = 0.001); however, they had a lower risk of arrhythmia (2.7% vs. 5.8%; p = 0.027).

Infant pulmonary function tests in individuals with Down syndrome.

BACKGROUND AND OBJECTIVE: Down syndrome is associated with significant respiratory morbidity. The available pulmonary function testing data in school aged children and adults with Down show evidence of restrictive lung disease. We aimed to evaluated infant pulmonary function tests (iPFTs) in individuals with Down. METHODS: An observational case-control study evaluating iPFTs results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in Infants with Down were compared to a spirometry control group of infants with normal expiratory airflows, using the Mann-Whitney U and Fisher's exact tests. RESULTS: iPFT data from 66 infants (20 Down and 46 control) were evaluated in the study. Most infants with Down showed abnormalities of an obstructive lung disease with mildly increased lung volumes and significantly decreased expiratory flows, mostly unresponsive to bronchodilators. Airflow limitations were most prominent at low lung volumes (median (IQR); maximal expiratory flow at functional residual capacity, V˙max FRC = 48 (26-78) %predicted in Down Vs. V˙max FRC = 100 (93-114) %predicted in controls, p < 0.001). We further observed an alteration in breathing mechanics with significantly decreased respiratory system compliance and increased airway resistance associated with decreased tidal volumes but similar minute ventilation. CONCLUSION: Our study shows that infants with have a fixed airflow obstruction phenotype. These results add comprehensive data to allow better understanding of the lung disease present early in life of infants with Down syndrome. Further studies are required to improve management of respiratory disease in individuals with Down.

Altered lung physiology in two cohorts after COVID-19 infection as assessed by computed cardiopulmonography.

The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O2. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po2 gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease.NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.

Differences in the Measurement of Functional Residual Capacity Between Body Plethysmographs of Two Manufacturers.

Body plethysmography is a fundamental method for the assessment of static lung volumes. Although equipment is provided by several manufacturers, there are no established cross-vendor tools for quality control. In the process of quality control and analysis of data on hyperinflation from the large COPD cohort COSYCONET, hints appeared that plethysmographs of different vendors might yield different values for static lung volumes. Functional residual capacity (FRC) differed about 0.67 litres between plethysmographs of the manufacturer Vyaire and Ganshorn. Absolute differences of residual lung volume (RV) and total lung capacity (TLC) were similar. It appears undeniable that differences of this magnitude have an impact on clinical interpretation. Thus, device harmonization seems to be required.

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

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

Sensitive physiological readouts to evaluate countermeasures for lipopolysaccharide-induced lung alterations in mice.

Despite decades of research, studies investigating the physiological alterations caused by an acute bout of inflammation induced by exposing the lung to lipopolysaccharide have yielded inconsistent results. This can be attributed to small effects and/or a lack of fitted physiological testing. Herein, a comprehensive investigation of lung mechanics was conducted on 270 male C57BL/6 mice at 24, 48, or 96 h after an intranasal exposure to saline or lipopolysaccharide at either 1 or 3 mg/kg (30 mice per group). Traditional techniques that probe the lung using small-amplitude perturbations (i.e., oscillometry) were used, together with less conventional and new techniques that probe the lung using maneuvers of large amplitudes. The latter include a partial and a full-range pressure-volume maneuvers to measure quasi-static elastance, compliance, total lung volume, vital capacity, and residual volume. The results demonstrate that lung mechanics assessed by oscillometry was only slightly affected by lipopolysaccharide, confirming previous findings. In contradistinction, lipopolysaccharide markedly altered mechanics when the lung was probed with maneuvers of large amplitudes. With the dose of 3 mg/kg at the peak of inflammation (48 h postexposure), lipopolysaccharide increased quasi-static elastance by 26.7% (P < 0.0001) and decreased compliance by 34.5% (P < 0.0001). It also decreased lung volumes, including total lung capacity, vital capacity, and residual volume by 33.3%, 30.5%, and 43.3%, respectively (all P < 0.0001). These newly reported physiological alterations represent sensitive outcomes to efficiently evaluate countermeasures (e.g., drugs) in the context of several lung diseases.