Origins of Racial and Ethnic Bias in Pulmonary Technologies.

Understanding how biases originate in medical technologies and developing safeguards to identify, mitigate, and remove their harms are essential to ensuring equal performance in all individuals. Drawing upon examples from pulmonary medicine, this article describes how bias can be introduced in the physical aspects of the technology design, via unrepresentative data, or by conflation of biological with social determinants of health. It then can be perpetuated by inadequate evaluation and regulatory standards. Research demonstrates that pulse oximeters perform differently depending on patient race and ethnicity. Pulmonary function testing and algorithms used to predict healthcare needs are two additional examples of medical technologies with racial and ethnic biases that may perpetuate health disparities.

Identification of Idiopathic Pulmonary Fibrosis and Prediction of Disease Severity via Machine Learning Analysis of Comprehensive Metabolic Panel and Complete Blood Count Data.

BACKGROUND: Diagnosis of idiopathic pulmonary fibrosis (IPF) typically relies on high-resolution computed tomography imaging (HRCT) or histopathology, while monitoring disease severity is done via frequent pulmonary function testing (PFT). More reliable and convenient methods of diagnosing fibrotic interstitial lung disease (ILD) type and monitoring severity would allow for early identification and enhance current therapeutic interventions. This study tested the hypothesis that a machine learning (ML) ensemble analysis of comprehensive metabolic panel (CMP) and complete blood count (CBC) data can accurately distinguish IPF from connective tissue disease ILD (CTD-ILD) and predict disease severity as seen with PFT. METHODS: Outpatient data with diagnosis of IPF or CTD-ILD (n = 103 visits by 53 patients) were analyzed via ML methodology to evaluate (1) IPF vs CTD-ILD diagnosis; (2) %predicted Diffusing Capacity of Lung for Carbon Monoxide (DLCO) moderate or mild vs severe; (3) %predicted Forced Vital Capacity (FVC) moderate or mild vs severe; and (4) %predicted FVC mild vs moderate or severe. RESULTS: ML methodology identified IPF from CTD-ILD with AUCTEST = 0.893, while PFT was classified as DLCO moderate or mild vs severe with AUCTEST = 0.749, FVC moderate or mild vs severe with AUCTEST = 0.741, and FVC mild vs moderate or severe with AUCTEST = 0.739. Key features included albumin, alanine transaminase, %lymphocytes, hemoglobin, %eosinophils, white blood cell count, %monocytes, and %neutrophils. CONCLUSION: Analysis of CMP and CBC data via proposed ML methodology offers the potential to distinguish IPF from CTD-ILD and predict severity on associated PFT with accuracy that meets or exceeds current clinical practice.

A comparative study of bronchodilator response: utilizing pre-bronchodilator versus predicted normal values.

BACKGROUND: A positive bronchodilator response has been defined as a 12% increase in the forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) from their respective pre-bronchodilator values, combined with at least a 0.2 L absolute change. Recent recommendations suggested the use of the percent change in FEV1 and FVC relative to their predicted normal values without having applied them in patients with airflow obstruction. The aim of the current study was to compare the two approaches over a wide range of pre-bronchodilator FEV1 and FVC values. METHODS: A retrospective review of consecutive patients undergoing spirometry and bronchodilator testing was completed. The change in FEV1 and FVC with a bronchodilator was expressed relative to the pre-bronchodilator and predicted normal FEV1 and FVC. RESULTS: In 1,040 patients with a non-paradoxical change in FEV1, 19.0% had a ≥ 12% change in FEV1 using their pre-bronchodilator value compared to 5.7% using their predicted normal value. For FVC, the respective values were 12.7% vs. 5.8%. The difference was retained in patients with a ≥ 0.2 L change in FEV1 or FVC. In unobstructed patients, the upper threshold (two standard deviations above the mean) of the bronchodilator response was 14% for FEV1 and 10% for FVC using predicted normal values. CONCLUSIONS: Expressing the percent change in FEV1 and FVC relative to predicted normal values reduces the over-estimation of the bronchodilator response, especially in patients with a very low pre-bronchodilator FEV1, including in those with a ≥ 0.2 L change in FEV1. Irrespective of pre-bronchodilator values, a ≥ 14% change in FEV1 and ≥ 10% change in FVC relative to the predicted normal values could be considered a positive bronchodilator response.

The total-breath method yields higher values of DLCO and TLC than the conventional method.

BACKGROUND: The 2017 ATS/ERS technical standard for measuring the single-breath diffusing capacity (DLCO) proposed the "rapid-gas-analyzer" (RGA) or, equivalently, "total-breath" (TB) method for the determination of total lung capacity (TLC). In this study, we compared DLCO and TLC values estimated using the TB and conventional method, and how estimated TLC using these two methods compared to that determined by body plethysmography. METHOD: A total of 95 people with COPD (GOLD grades 1-4) and 23 healthy subjects were studied using the EasyOne Pro (ndd Medical Technologies, Switzerland) and Master Screen Body (Vyaire Medical, Höchberg, Germany). RESULTS: On average the TB method resulted in higher values of DLCO (mean ± SD Δ = 0.469 ± 0.267; 95%CI: 0.420; 0.517 mmol*min-1*kPa-1) and TLC (Δ = 0.495 ± 0.371; 95%CI: 0.427; 0.562 L) compared with the conventional method. In healthy subjects the ratio between TB and conventional DLCO was close to one. TLC estimated using both methods was lower than that determined by plethysmography. The difference was smaller for the TB method (Δ = 1.064 ± 0.740; 95%CI: 0.929; 1.199 L) compared with the conventional method (Δ = 1.558 ± 0.940; 95%CI: 1.387; 1.739 L). TLC from body plethysmography could be estimated as a function of TB TLC and FEV1 Z-Score with an accuracy (normalized root mean square difference) of 9.1%. CONCLUSION: The total-breath method yielded higher values of DLCO and TLC than the conventional analysis, especially in subjects with COPD. TLC from the total-breath method can also be used to estimate plethysmographic TLC with better accuracy than the conventional method. The study is registered under clinicaltrial.gov NCT04531293.

Resting diffusing capacity and severity of radiographic disease predict gas exchange abnormalities with exercise in former US coal miners.

BACKGROUND: The US Department of Labor (DOL) does not fund diffusing capacity (DLCO) or metabolic measurements from cardiopulmonary exercise testing (CPET) for coal miners' disability evaluations. Although exercise arterial blood gas testing is covered, many miners are unable to perform maximal tests, and sampling at peak exercise can be challenging. We explored the relationship between resting DLCO, radiographic disease severity, and CPET abnormalities in former US coal miners. METHODS: We analyzed data from miners evaluated between 2005 and 2015. Multivariable linear and logistic regression analyses were used to examine relationships between percent predicted (pp) forced expiratory volume in 1 s (FEV1pp), DLCOpp, VO2maxpp, A-a oxygen gradient (A-a)pp, dead space fraction (Vd/Vt), disabling oxygen tension (PO2), and radiographic findings of pneumoconiosis. RESULTS: Data from 2015 male coal miners was analyzed. Mean tenure was 28 years (SD 8.6). Thirty-twopercent had an abnormal A-a gradient (>150 pp), 20% had elevated Vd/Vt (>0.33), and 34% a VO2max < 60 pp. DLCOpp strongly predicted a disabling PO2, with an odds ratio (OR) of 2.33 [2.09-2.60], compared to 1.18 [1.08-1.29] for FEV1. Each increase in subcategory of small opacity (simple) pneumoconiosis increased the odds of a disabling PO2 by 42% [1.29-1.57], controlling for age, body mass index, pack-years of tobacco smoke exposure, and years of coal mine employment. CONCLUSIONS: DLCO is the best resting pulmonary function test predictor of CPET abnormalities. Radiographic severity of pneumoconiosis was also associated with CPET abnormalities. These findings support funding DLCO testing for impairment and suggest the term "small opacity" should replace "simple" pneumoconiosis to reflect significant associations with impairment.

Lung Function in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Prior studies have found that human immunodeficiency virus (HIV) infection is associated with impaired lung function and increased risk of chronic lung disease, but few have included large numbers of women. In this study, we investigate whether HIV infection is associated with differences in lung function in women. METHODS: This was a cross-sectional analysis of participants in the Women's Interagency HIV Study, a racially and ethnically diverse multicenter cohort of women with and without HIV. In 2018-2019, participants at 9 clinical sites were invited to perform spirometry. Single-breath diffusing capacity for carbon monoxide (DLCO) was also measured at selected sites. The primary outcomes were the post-bronchodilator forced expiratory volume in 1 second (FEV1) and DLCO. Multivariable regression modeling was used to analyze the association of HIV infection and lung function outcomes after adjustment for confounding exposures. RESULTS: FEV1 measurements from 1489 women (1062 with HIV, 427 without HIV) and DLCO measurements from 671 women (463 with HIV, 208 without HIV) met standards for quality and reproducibility. There was no significant difference in FEV1 between women with and without HIV. Women with HIV had lower DLCO measurements (adjusted difference, -0.73 mL/min/mm Hg; 95% confidence interval, -1.33 to -.14). Among women with HIV, lower nadir CD4 + cell counts and hepatitis C virus infection were associated with lower DLCO measurements. CONCLUSIONS: HIV was associated with impaired respiratory gas exchange in women. Among women with HIV, lower nadir CD4 + cell counts and hepatitis C infection were associated with decreased respiratory gas exchange.

A 5-year follow-up of pulmonary function tests in childhood-onset systemic lupus erythematosus: a single-center retrospective study.

SIGNIFICANCE: Pulmonary involvement in childhood-onset systemic lupus erythematosus (cSLE), contributes to significant morbidity and mortality. Manifestations include chronic interstitial pneumonitis, pneumonia, pleuritis, alveolar hemorrhage, and shrinking lung syndrome. However, many patients can be asymptomatic from a respiratory standpoint and still have pulmonary function test (PFT) abnormalities. Our aim is to describe PFT abnormalities in patients with cSLE. METHODS: We completed a retrospective review of 42 patients with cSLE followed at our center. These patients were at least 6 years old (so they could complete PFTs). We collected data from July 2015 to July 2020. RESULTS: Out of the 42 patients, 10 (23.8%) had abnormal PFTs. These 10 patients had a mean age at diagnosis of 13 ± 2.9 years. Nine were female. One-fifth (20%) self-identified as Hispanic, 20% as Asian, 10% as Black or African American, and the remaining 50% as "Other." Of the 10, 3 had restrictive disease only, 3 with diffusion impairment only, and 4 with both restrictive lung disease and diffusion impairment. Patients with restrictive patterns had a mean total lung capacity (TLC) of 72.5 ± 5.8 throughout the study period. The average diffusing capacity for carbon monoxide corrected for hemoglobin (DsbHb) among patients with diffusion limitation during the study period was 64.8 ± 8.3. CONCLUSIONS: The most common PFT abnormalities seen in patients with cSLE are alterations in diffusing capacity as well as restrictive lung disease.

Does the severity of asthma affect exercise capacity and daily physical activity?

OBJECTIVE: Exercise capacity, daily physical activity, and psychological profile are crucial aspects in the management of asthmatic patients. Whether these features are expressed in a different way in mild-moderate (MMA) and severe asthma (SA) is unknown. METHODS: In this observational cross-sectional study, patients matching the American Thoracic Society/European Respiratory Society (ATS/ERS) definition for SA underwent incremental cardiopulmonary exercise testing (CPET), full lung function testing, and an evaluation of daily step count and physical activity. Questionnaires on quality of life, general fatigue, and presence of anxiety and depression traits (Hospital Anxiety and Depression Scale - HADS) were administered. Patients were compared with a cohort of age- and gender-matched MMA patients. RESULTS: We enrolled 16 SA, 17 MMA patients, and 16 healthy subjects. Compared to MMA, SA subjects showed a median (interquartile range) reduced peak oxygen consumption during CPET (20.4 (17.2-23.3) vs. 25.6 (18.5-30.3) ml/min/kg; p = 0.019), a reduced resting lung function (FEV1% of predicted 77 (67-84) vs. 96 (84-100); p < 0.001) and a pronounced anxiety trait at HADS (9.5 (3-11.7) vs. 4.0 (2.0-7.5); p = 0.023). In addition, SA patients showed a significantly higher reduction in inspiratory capacity from rest to peak (310 (160-520) vs. 110 (-65-325) ml; p = 0.031). We found no significant differences in mean daily step count or quality of life. CONCLUSIONS: Compared to MMA, SA patients present a reduced exercise capacity and a more pronounced anxiety trait, but not worse daily physical activity or quality of life. These aspects should be considered in the clinical management and research development of SA.

The Role of Pulmonary Function Testing and Lung Imaging in the Long-Term Follow-Up of Patients with COVID-19 Pneumonia.

BACKGROUND: Post-COVID-19 Interstitial Lung Disease (PC-ILD) is characterized by fibrotic-like signs at high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) abnormalities after SARS-CoV-2 infection. It is still not clear how frequent these tests should be performed to rule out long-term consequences of COVID-19 pneumonia. OBJECTIVES: The aims of our study were to evaluate the incidence and risk factors of PC-ILD and possibly to propose a long-term follow-up program. METHOD: One-hundred patients, hospitalized in our ward for moderate to critical COVID-19, underwent two follow-up visits at three and 15 months in which PFTs and HRCT were performed. RESULTS: At the 15-month follow-up, 8% of patients showed residual radiological and functional signs consistent with PC-ILD. All but one of these patients had already demonstrated PFTs and HRCT alterations at first follow-up visit, and the last 1 patient showed worsening of lung function during follow-up. These findings highlight the negative predictive value of PFTs at 3-month follow-up for the development of PC-ILD. Aging, severity of COVID-19, and degree of pulmonary involvement during acute infection proved to be significant risk factors for developing PC-ILD. CONCLUSIONS: Our study highlights the importance of PFTs in the long-term follow-up of patients affected by moderate to critical COVID-19 pneumonia. Further studies are needed to confirm our hypothesis that HRCT should be performed only in patients with PFTs abnormalities.

Predictors of methacholine challenge testing results in subjects without airflow obstruction.

OBJECTIVE: Methacholine challenge testing (MCT) is considered when asthma remains clinically suspected despite normal spirometry. Few studies have attempted to determine the predictive factors of MCT results. We aimed to establish which demographic data, clinical symptoms, pulmonary function testing results, and laboratory values were associated with abnormal MCT (provocation concentration causing a 20% decrease in FEV1 (PC20) ≤ 16 mg/mL) in subjects without airflow obstruction on spirometry. METHODS: All patients who completed MCT at Montfort Hospital between January 1st, 2016 and December 31st, 2018 were identified. Subjects with a reduced FEV1/FVC ratio were excluded. We used Pearson's chi-squared test and point-biserial correlation method to determine which variables had a significant relationship (p < 0.05) with MCT results. RESULTS: 23.3% of patients who underwent MCT had airflow limitation. In the 1126 subjects with a normal FEV1/FVC ratio, PC20 ≤ 16 mg/mL was found in 13.0%. Younger age, female gender, body mass index ≥ 40, and reported wheezing were factors associated with increased probability of airway hyper responsiveness. Lower FEV1, significant improvement of the FEV1 post-bronchodilator, reduced FEF25%-75%, greater FEF25%-75% reversibility, airway resistance measurements above the upper limit of normal, and increased blood eosinophil counts were predictive of abnormal MCT. CONCLUSIONS: Only 13.0% of patients referred for MCT had a PC20 ≤ 16 mg/mL when the FEV1/FVC ratio was normal, highlighting the need to further define in which individuals this test is truly warranted. Further investigation is required to develop an easy-to-use and validated prediction model in order to better understand patients' pretest probability of abnormal MCT.

Angle ß combined with FeNO and FEV1/FVC% for the detection of asthma in school-aged children.

OBJECTIVE: The diagnostic value of angle ß in school-aged children with asthma is unknown. We speculate that angle ß may reflect diversification of the forced expiratory flow (FEF) to some extent. The objective of this study was to assess the diagnostic accuracy of angle ß, FeNO, pulmonary function parameters and their combinations for asthma in school-aged children. METHODS: In total, 248 children participated in this study (140 children with asthma and 108 healthy children). The diagnostic performance of angle ß, FeNO and pulmonary function parameters was determined using receiver operating characteristic (ROC) curves. In the ROC analysis, we used the hold out cross-validation method to avoid overfitting. This study was performed in China and followed the Guidelines for the diagnosis and optimal management of asthma in children (China). RESULTS: 1) In the asthma group, the mean angle ß value was significantly smaller than that in the control group (P < 0.001), but the mean FeNO value was significantly higher than that in the control group (P < 0.001). 2) More acute exacerbation or greater severity corresponded to a smaller angle ß. 3) Among the single indices, the area under the ROC curve of angle ß was the largest (except for FEV1/FVC%). For combined indicators, after cross-verification, the combination of angle ß, FEV1/FVC% and FeNO showed the highest diagnostic accuracy. CONCLUSION: Angle ß combined with FeNO and FEV1/FVC% can improve the diagnostic accuracy for asthma in school-aged children.

Abnormal Pulmonary Function in Early Parkinson's Disease: A Preliminary Prospective Observational Study.

Early Parkinson's disease (PD) may cause respiratory dysfunction; however the findings vary among studies. The aim of the preliminary prospective observational study was to explore the deterioration of pulmonary function at various stages in patients with early PD. A total of 237 patients with PD were screened. Fifty-six patients were included (modified Hoehn and Yahr stage ≤ 2.5). In addition, 56 age-matched healthy controls were also included in the study. Significant differences between the PD and control groups were found in all the investigated lung-function parameters. The maximal voluntary ventilation (MVV) percent predicted was the only parameter that distinguished PD stages (101.1 ± 14.9% vs. 82.8 ± 19.2% vs. 71.4 ± 12.9%, Hoehn and Yahr stages 1.5 vs. 2 vs. 2.5, respectively; p < 0.005). MVV could be the most sensitive parameter for distinguishing the severity of early-stage PD.

Practices and Procedures in Clinical Pediatric Exercise Laboratories in North America.

Interinstitutional differences in clinical pediatric exercise laboratory (CPEL) practices may affect patient care and efficacy of multicenter research. PURPOSE: To describe current practices/procedures in CPELs and explore differences in CPELs employing exercise physiologists to those that do not. METHODS: A 40-item survey was distributed to CPELs in North America focusing on (1) staffing; (2) exercise stress testing (EST) volumes, reporting, and interpretation; and (3) EST procedures/protocols. RESULTS: Of the 55 responses, 89% were in the United States, 85% were children's hospitals with university affiliation, and 58% were cardiology specific. Exercise physiologists were employed in 56% of CPELs, and 78% had master's degrees or higher. Certifications were required in most CPELs (92% emergency life-support, 27% professional, and 21% clinical). Median volume was 201 to 400 ESTs per year, 80% used treadmill, and 10% used cycle ergometer as primary modalities. Ninety-three percent of CPELs offered metabolic ESTs, 87% offered pulmonary function testing, 20% used institution-specific EST protocols, and 72% offered additional services such as cardiac/pulmonary rehabilitation. CPELS staffing exercise physiologists performed higher volumes of ESTs (P = .004), were more likely to perform metabolic ESTs (P = .028), participated in more research (P < .001), and provided services in addition to ESTs (P = .001). CONCLUSIONS: Heterogeneity in CPELs staffing and operation indicates need for standardization.

The Impact of an Electronic Health Record Intervention on Spirometry Completion in Patients with Chronic Obstructive Pulmonary Disease.

Spirometry is necessary to diagnose chronic obstructive pulmonary disease (COPD), yet a large proportion of patients are diagnosed and treated without having received testing. This study explored whether the effects of interventions using the electronic health record (EHR) to target patients diagnosed with COPD without confirmatory spirometry impacted the incidence rates of spirometry referrals and completions. This retrospective before and after study assessed the impact of provider-facing clinical decision support that identified patients who had a diagnosis of COPD but had not received spirometry. Spirometry referrals, completions, and results were ascertained 1.5 years prior to and 1.5 years after the interventions were initiated. Inhaler prescriptions by class were also tallied. There were 10,949 unique patients with a diagnosis of COPD who were eligible for inclusion. 4,895 patients (44.7%) were excluded because they had completed spirometry prior to the cohort start dates. The pre-intervention cohort consisted of 2,622 patients, while the post-intervention cohort had 3,392. Spirometry referral rates pre-intervention were 20.2% compared to 31.6% post-intervention (p < 0.001). Spirometry completion rates rose from 13.2% pre-intervention to 19.3% afterwards (p < 0.001). 61.7% (585 of 948) had no evidence of airflow obstruction. After excluding patients with a diagnosis of asthma, 25.8% (126 of 488) patients who had no evidence of airflow obstruction had prescriptions for long-acting bronchodilators or inhaled steroids. A concerted EHR intervention modestly increased spirometry referral and completion rates in patients with a diagnosis of COPD without prior spirometry and decreased misclassification of disease.

Lung function assessment in the Pacific walrus (Odobenus rosmarus divergens) while resting on land and submerged in water.

In the present study, we examined lung function in healthy resting adult (born in 2003) Pacific walruses (Odobenus rosmarus divergens) by measuring respiratory flow ([Formula: see text]) using a custom-made pneumotachometer. Three female walruses (670-1025 kg) voluntarily participated in spirometry trials while spontaneously breathing on land (sitting and lying down in sternal recumbency) and floating in water. While sitting, two walruses performed active respiratory efforts, and one animal participated in lung compliance measurements. For spontaneous breaths, [Formula: see text] was lower when walruses were lying down (e.g. expiration: 7.1±1.2 l s-1) as compared with in water (9.9±1.4 l s-1), while tidal volume (VT, 11.5±4.6 l), breath duration (4.6±1.4 s) and respiratory frequency (7.6±2.2 breaths min-1) remained the same. The measured VT and specific dynamic lung compliance (0.32±0.07 cmH2O-1) for spontaneous breaths were higher than those estimated for similarly sized terrestrial mammals. VT increased with body mass (allometric mass-exponent=1.29) and ranged from 3% to 43% of the estimated total lung capacity (TLCest) for spontaneous breaths. When normalized for TLCest, the maximal expiratory [Formula: see text] ([Formula: see text]exp) was higher than that estimated in phocids, but lower than that reported in cetaceans and the California sea lion. [Formula: see text]exp was maintained over all lung volumes during spontaneous and active respiratory manoeuvres. We conclude that location (water or land) affects lung function in the walrus and should be considered when studying respiratory physiology in semi-aquatic marine mammals.

Does lung function change in the months after an asthma exacerbation in children?

BACKGROUND: There are limited data describing lung function changes in children after an asthma exacerbation. Our hypothesis was that lung function does not fully recover in children in the months following an asthma exacerbation. METHODS: We used a data set of children with asthma where lung function (including FEV1 , FEV1 /FVC ratio and FEF25-75 ) was measured at 3-month intervals over a year. Mixed-level models compared spirometry measured on two occasions 3 months apart before a single exacerbation (assessments 1 and 2) with measurements made on two occasions after the exacerbation (assessments 3 and 4), with adjustment for covariates. Changes in spirometry over a year were also analysed across those with exacerbations in no, one or more than one 3-month periods. RESULTS: For the 113 children who had a single exacerbation, spirometry measured at assessments 1 or 2 did not differ from measurements at assessments 3 or 4 when the whole population was considered. When stratified into tertiles by change in %FEV1 between assessments 2 and 3, those with the greater reduction were more likely to be treated with long-acting beta-agonist, but in this category, %FEV1 at assessment 4 had returned to the value at assessment 1. %FEV1 did not change over a 12-month period within and between the three exacerbation categories (n = 809). CONCLUSION: One or more asthma exacerbation was not associated with a fall in lung function for the whole population. In a subset of individuals, lung function does fall after an exacerbation but returns to pre-exacerbation values after a period of months.

Utility and efficiency of methacholine challenge testing in evaluating pediatric asthma: unraveling the diagnostic conundrum.

OBJECTIVE: Interpretation of methacholine challenge testing (MCT) results depends on the patient's pretest probability of asthma as well as the provocative concentration (PC20); however, ordering providers rarely understand the complexity associated with its interpretation. This study investigated the clinical utility and efficiency of MCT at a tertiary center in evaluating pediatric asthma. METHODS: Retrospective chart review was done for all MCT done at a tertiary center over a six year period (2011-2017). Demographics, referring provider, referral diagnosis, current symptoms with and without exercise, and baseline spirometry were collected. Pretest probability of asthma was assigned by author (RB) who was blinded to MCT results and PC20. Post-test probability of asthma was assigned based on pretest probability, MCT result (+/-), and PC20. Three assigned asthma probability categories were "unlikely" "likely", and "very likely". RESULTS: Of 172 subjects (91 Females, age range 5-21 years), 64.9% of MCT results (n = 111)) were negative and 35.1% (n = 60)) were positive. One was inconclusive. Those who tested positive were shorter, lighter, younger and had lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio than those who tested negative (p < 0.05). Subjects with exercise symptoms only were less likely to test positive (OR 0.2, CI 0.1-0.5). In a majority of subjects (91.8%; 157/171), MCT increased the certainty of presence or absence of asthma. CONCLUSIONS: In our subject population, MCT could be useful in evaluating pediatric asthma if subject's pretest probability of asthma and PC20 was taken into account. It was not as useful for subjects with exercise symptoms only.

Pulmonary Function Testing in Patients with Tracheostomies: Feasibility and Technical Considerations.

PURPOSE: Pulmonary function testing (PFT) in patients with tracheostomies has been perceived as difficult to perform and clinically unreliable. We studied the feasibility, quality, repeatability and clinical significance of PFT. METHODS: Patients with tracheostomies that underwent PFT from January 1, 2010 to February 29, 2012 were identified. Clinical history and PFT data were reviewed retrospectively. RESULTS: Fifty patients (88% men) were identified. Forty-seven (94%) patients were able to perform PFT. Acceptable repeatability was obtained for FVC in 39 (83%) and for FEV1 in 41 (87%). Patients with tracheostomies showed difficulty in meeting ATS end-of-test criteria; only 9 (19%) met plateau criteria and 25 (53%) had exhalation times of greater than 6 s. Obstructive pattern was observed in 30 (64%) and restrictive pattern in 9 (19%). DLCO measurements were attempted in 43 patients and satisfactorily obtained in 34 (79%). CONCLUSIONS: PFT can be performed with reliability in patients with tracheostomies, and they are useful for detecting and classifying types of lung dysfunction.

Noninvasive Measurement of Pulmonary Function in Experimental Mouse Models of Airway Disease.

Mouse models have become an indispensable tool in translational research of human airway disease and have provided much of our understanding of the pathogenesis of airway disease such as asthma. In these models the ability to assess pulmonary function and particularly airway responsiveness is critically important. Existing methods for testing pulmonary function in mice in vivo include noninvasive and invasive technologies. Noninvasive head-out body plethysmography is a well-established and widely accepted technique which has been proven as a reliable method to measure lung function on repeated occasions in intact, conscious mice. We have performed several validation studies in allergic mice to compare the parameter midexpiratory flow (EF50) as a noninvasive marker of airflow limitation with invasively measured gold standard parameters of lung mechanics. The results of these studies showed a good agreement of EF50 with the invasive assessment of lung resistance and dynamic compliance with a somewhat lower sensitivity of EF50. The measurement of EF50 together with basic respiratory parameters is particularly appropriate for simple and repeatable screening of pulmonary function in large numbers of mice or if noninvasive measurement without use of anesthesia is required. Beyond known applications, head-out body plethysmography also provides a much-needed high-throughput screening tool to gain insights into the impact and kinetics of respiratory infections such as SARS-COV-2 on lung physiology in laboratory mice.

Perinatal inflammation relates to early respiratory morbidity and lung function at 12 years of age in children born very preterm.

AIM: Very preterm birth may be associated with lung function impairment later in life. It is not known if this is caused by prematurity per se or by associated perinatal events, such as maternal-foetal inflammation and severity of early neonatal lung disease. We assessed these factors in a prospective cohort of very preterm infants followed from birth to middle school age. METHODS: In 71 infants with a gestational age of median 27.4 (range 23.9-31.7) weeks, pro-inflammatory and modulatory cytokines were measured in umbilical cord blood and in arterial blood sampled at 6, 24 and 72 h after birth, and cumulated cytokine concentrations were calculated as area under the curve (AUC). At median 12.6 (range 12.3-13.5) years of age, pulmonary function testing was done in 53 children. RESULTS: There was a positive correlation between days on mechanical ventilation and AUC for IL-6 (p = 0.001), IL-8 (p = 0.015) and IL-10 (p = 0.006). Infants with bronchopulmonary dysplasia (BPD; n = 32) had higher AUC for the cytokines IL-6, IL-8 and IL-10 than those without BPD (all p < 0.01). Higher levels of AUC for IL-6 at birth correlated with lower forced expiratory volume in 1 s (p = 0.030) and lower mean expiratory flow rate between 25 and 75% of forced vital capacity (p = 0.034). CONCLUSION: Perinatal inflammation, assessed by circulating cytokines in the first three days of life, was associated with BPD and with airway obstruction at 12 years of age.