Proteomic associations with forced expiratory volume: a Mendelian randomisation study.

BACKGROUND: A decline in forced expiratory volume (FEV1) is a hallmark of respiratory diseases that are an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. METHODS: Data from the population-based AGES-Reykjavik study were used. Serum proteomic measurements were done using 4782 DNA aptamers (SOMAmers). Data from 1479 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional two-sample Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). RESULTS: In observational analyses, 530 SOMAmers were associated with FEV1 after multiple testing adjustment (FDR < 0.05). The most significant were Retinoic Acid Receptor Responder 2 (RARRES2), R-Spondin 4 (RSPO4) and Alkaline Phosphatase, Placental Like 2 (ALPPL2). Of the 257 SOMAmers with genetic instruments available, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta (ERO1B) and Apolipoprotein M (APOM). THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. CONCLUSIONS: In summary, this large scale proteogenomic analyses of FEV1 reveals circulating protein markers of FEV1, as well as several proteins with potential causality to lung function.

Associations of personal urinary volatile organic compounds and lung function in children.

BACKGROUND: We investigated the correlation between urine VOC metabolites and airway function in children exposed to anthropogenic volatile organic compounds (VOCs), notable pollutants impacting respiratory health. METHODS: Out of 157 respondents, 141 completed skin prick tests, spirometry, IOS, and provided urine samples following the International Study of Asthma and Allergies in Childhood (ISAAC)-related questions. Allergic sensitization was assessed through skin prick tests, and airway functions were evaluated using spirometry and impulse oscillometry (IOS). Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) was recorded and FEV1/FVC ratio was calculated. Airway mechanics parameters including respiratory resistance at 5 Hz (Rrs5) mean respiratory resistance between 5 Hz and 20 Hz (Rrs5-20), were also recorded. Urine concentrations of metabolites of benzene, ethylbenzene, toluene, xylene, styrene, formaldehyde, carbon-disulfide were analyzed by gas chromatography/tandem mass spectroscopy. RESULTS: The median age at study participation was 7.1 (SD 0.3) years. Muconic acid (benzene metabolites) and o-methyl-hippuric acid (xylene metabolites) above medians were associated with a significant increase in Rrs5 (muconic acid: aß = 0.150, p = .002; o-methyl-hippuric acid: aß = 0.143, p = .023) and a decrease in FEV1/FVC (o-methyl-hippuric acid: aß = 0.054, p = .028) compared to those below median. No associations were observed for Rrs5-20 and FEV1 between the groups categorized as above and below the median (all parameter p values > .05). CONCLUSIONS: Elevated levels of benzene and xylene metabolites were associated with a significant increase in Rrs5 and a decrease in FEV1/FVC, related to increased resistance and restrictive lung conditions compared to individuals with concentrations below the median.

Comparison of different reference values for lung function: implications of inconsistent use among centers.

BACKGROUND: For interpretation of pulmonary function tests (PFTs), reference values based on sex, age, height and ethnicity are needed. In Norway, the European Coal and Steel Community (ECSC) reference values remain widely used, in spite of recommendations to implement the more recent Global Lung Function Initiative (GLI) reference values. OBJECTIVE: To assess the effects of changing from ECSC to GLI reference values for spirometry, DLCO and static lung volumes, using a clinical cohort of adults with a broad range in age and lung function. METHODS: PFTs from 577 adults (18-85 years, 45% females) included in recent clinical studies were used to compare ECSC and GLI reference values for FVC, FEV1, DLCO, TLC and RV. Percent predicted and lower limit of normal (LLN) were calculated. Bland-Altman plots were used to assess agreement between GLI and ECSC % predicted values. RESULTS: In both sexes, GLI % predicted values were lower for FVC and FEV1, and higher for DLCO and RV, compared to ECSC. The disagreement was most pronounced in females, with mean (SD) difference 15 (5) percent points (pp) for DLCO and 17 (9) pp for RV (p < 0.001). With GLI, DLCO was below LLN in 23% of the females, with ECSC in 49% of the females. CONCLUSIONS: The observed differences between GLI and ECSC reference values are likely to entail significant consequences with respect to criteria for diagnostics and treatment, health care benefits and inclusion in clinical trials. To ensure equity of care, the same reference values should be consistently implemented across centers nationwide.

Unmasking a Silent Threat: Improving Pulmonary Hypertension Screening Methods for Interstitial Lung Disease Patients.

This article provides a comprehensive overview of the latest literature on the diagnostics and treatment of pulmonary hypertension (PH) associated with interstitial lung disease (ILD). Heightened suspicion for PH arises when the advancement of dyspnoea in ILD patients diverges from the expected pattern of decline in pulmonary function parameters. The complexity of PH associated with ILD (PH-ILD) diagnostics is emphasized by the limitations of transthoracic echocardiography in the ILD population, necessitating the exploration of alternative diagnostic approaches. Cardiac magnetic resonance imaging (MRI) emerges as a promising tool, offering insights into hemodynamic parameters and providing valuable prognostic information. The potential of biomarkers, alongside pulmonary function and cardiopulmonary exercise tests, is explored for enhanced diagnostic and prognostic precision. While specific treatments for PH-ILD remain limited, recent studies on inhaled treprostinil provide new hope for improved patient outcomes.

Effect of Short-Term Treatment with Continuous Positive Airway Pressure on Cardiopulmonary Exercise Tolerance, Pulmonary and Cardiac Function in Patients with Obstructive Sleep Apnea.

Background: Obstructive sleep apnea (OSA) is a condition with a high prevalence, linked to an increased risk of cardiovascular disease as well as increased morbidity and death. CPAP is currently considered the "gold standard" treatment for OSA, but more thorough research and testing are required to assess its efficacy on cardiopulmonary function. Objectives: To evaluate pulmonary function of OSA patients, cardiopulmonary exercise tolerance test (CPET) performance, cardiac magnetic resonance imaging (MRI) parameters, and polysomnographic changes before and after 3 months of CPAP therapy. Materials and methods: A total of 34 patients diagnosed with moderate or severe OSA, as well as 17 patients as a control group for the evaluation of the cardiac MRI, were included in this study. All the subjects were obese (body mass index (BMI) > 30 kg/m2). Lung function tests, CPETs, cardiac MRIs, and polysomnography were performed at the time of the study's enrolment before the initiation of the CPAP therapy and after 3 months of the CPAP treatment. Results: The patients' VO2max during the CPAP treatment tended to increase, but no statistical significance was found (before treatment it was 17.52 ± 3.79 mL/kg/min and after 3 months of treatment, it was 18.6 ± 3,4 mL/kg/min; p = 0.255). The CPAP treatment had positive effects on pulmonary ventilation at the anaerobic threshold (VEAT): 44.51 L/min (43.21%) during the baseline visit and 38.60 L/min (37.86%) after the 3-month treatment period (p = 0.028). The ventilator equivalent for the carbon dioxide slope (VE/VCO2) at peak exercise decreased from 23.47 to 20.63 (p = 0.042). The patients' pulmonary function tests were without abnormalities and did not change after treatment. When assessing cardiac the MRIs, the RV ejection fraction was lower in the OSA group compared to that of the control subjects (53.69 ± 8.91 and 61.35 ± 9.08, p = 0.016). Both LA and RA global longitudinal strains (GLS) improved after 3 months of treatment with CPAP (20.45 ± 7.25 and 26.05 ± 14.00, p = 0.043; 21.04 ± 7.14 and 26.18 ± 7.17, p = 0.049, respectively). Additionally, it was found that CPAP therapy led to statistical improvements in RV end-diastolic volume (164.82 ± 32.57 and 180.16 ± 39.09, p = 0.042). The AHI and oxygen desaturation index (ODI) significantly changed after 3 months of the initiation of the CPAP treatment (p = 0.049 and p = 0.001, respectively). The REM sleep duration decreased, while the duration of non-REM sleep increased after treatment initiation with CPAP (p = 0.016 and p = 0.017, respectively). Conclusions: Short-term CPAP treatment improves pulmonary ventilation, sleep efficiency, and sleep architecture. Significant alterations in both atrias' GLS and RV end-diastolic volume were observed after 3 months of treatment. Longer-term follow-up and a larger patient sample are needed to confirm the reproducibility of our results.

Pulmonary 99mTc-HMDP uptake correlates with restrictive ventilatory defects and abnormal lung reactance in transthyretin cardiac amyloidosis patients.

BACKGROUND: Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify 99mTc-hydroxy methylene diphosphonate (HMDP) lung retention in hereditary transthyretin (ATTRv) cardiac amyloidosis patients and to relate tracer uptake intensity to pulmonary function and aerobic capacity. METHODS: We prospectively enrolled 20 patients with biopsy-proven ATTRv cardiac amyloidosis and 20 control subjects. Cardiac involvement was confirmed by echocardiography and nuclear imaging using 99mTc-HMDP. Semi-quantitative analysis of the heart, rib and lung retention was assessed using a simple region of interest technique. Pulmonary function was evaluation by the means of whole-body plethysmography, diffusing capacity of the lung for carbon monoxide, forced oscillation technique and cardiopulmonary exercise testing. RESULTS: Pulmonary tracer uptake estimated by lung to rib retention ratio was higher in ATTRv amyloidosis patients compared with control subjects: median 0.62 (0.55-0.69) vs 0.51 (0.46-0.60); p = 0.014. Analysis of relation between lung 99mTc-HMDP retention and pulmonary function parameters shown statistically significant correlations with total lung volume (% predicted), lung reactance (Xrs 5 Hz) and peak VO2, suggesting total lung capacity restriction impaired elastic properties of the lung and poor aerobic capacity. CONCLUSION: Our study suggests that some grade of pulmonary retention of 99mTc-HMDP may occur in patients with cardiac ATTRv amyloidosis, which can elicit deleterious effects on patient's lung function and aerobic capacity.

Idiopathic pulmonary fibrosis: Physician and patient perspectives on the pathway to care from symptom recognition to diagnosis and disease burden.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that requires ongoing care and is associated with considerable socioeconomic burden. We evaluated the IPF care pathway from symptom recognition to treatment. We describe the impact of IPF on healthcare resource use (HCRU), quality of life (QoL) and work impairment, and report differences in patient and physician perspectives using real-world data from France, Germany, Japan and the United States. METHODS: Quantitative, point-in-time data were collected as part of the Adelphi IPF II Disease Specific Programme™. Physician-reported data (patient demographics, medical history, diagnoses, treatment) were matched to patient-reported data (HCRU, QoL, work impairment). HCRU was measured as physician visits and hospitalizations. QoL and work impairment were measured using the EuroQol-5 Dimensions (EQ-5D) and Work Productivity and Activity Impairment questionnaires. RESULTS: Overall, 244 physicians reported data on 1249 patients, 739 of whom self-reported data. Diagnostic delays of 0.8 (Germany) to 2.0 (Japan) years after symptom onset were reported; treatment initiation was further delayed. In all countries, patients more often reported symptoms in the survey than did their physicians. On average, patients underwent 7-10 clinical tests before diagnosis. Antifibrotic use increased from 57% (2016) to 69% (2019); only 50% of patients with moderate/severe IPF were satisfied with their treatment. The 12-month hospitalization rates were 24% (Japan) to 64% (United States). Patients reported low QoL (mean EQ-5D visual analogue scale: 61.7/100). CONCLUSION: Patients with IPF experience considerable diagnostic and treatment delays. More effective therapies and management are needed to reduce the disease burden.

Chronic respiratory symptoms and lung function parameters in large-scale wood factory workers in Addis Ababa, Ethiopia: a comparative cross-sectional study.

BACKGROUND: Occupational wood dust causes chronic respiratory health problems as well as a decline in lung function. However, data on the prevalence of chronic respiratory symptoms and lung function parameters among large-scale wood factories workers in Ethiopia producing furniture are limited. The objective of this study was to determine the prevalence of chronic respiratory symptoms, lung function measures, and associated factors among large-scale wood industry workers in Addis Ababa, Ethiopia. METHODS: An institution-based cross-sectional study was conducted among 232 wood workers and 232 controls. Participants for the study were selected using stratified and systematic sampling from soft drink and wood factories. The chronic respiratory symptoms were assessed using a modified American Thoracic Society (ATS) questionnaire, and lung function tests were performed using an Easy on PC spirometer in accordance with the ATS standards for spirometry. The data were imported into Epi-data version 4.4.2 and analyzed with SPSS version 23. Poisson regression, Multivariate linear regression and multivariable logistic regression analysis were used. RESULTS: The prevalence ratio of overall chronic respiratory symptoms was significantly higher among woodworkers (65.7%) compared to controls (23.3%) in this study (PR = 2.17, 95% CI: 1.51-3.12). Current chronic respiratory symptoms were associated with gender, and previous chronic respiratory disease. Woodworkers had significantly lower Forced vital capacity (FVC) and Forced expiratory volume in the first second (FEV1) when compared to controls. CONCLUSION: Woodworkers had a higher prevalence of chronic respiratory symptoms and lower lung function measures, which lowered lung capacity when compared to controls. To reduce workers' exposure to wood dust, engineering control methods should be implemented.

Determinants of lung function changes in athletic swimmers. A review.

AIM: To summarise lung function characteristics of athletic swimmers and discuss mechanisms explaining these changes while putting forward the lack of a clear understanding of the precise physiological factors implicated. METHODS: Literature search until 07.2021 on Medline and EMBASE using keywords swimming, athletes, respiratory physiology, lung development, lung function tests. Relevant articles in French and English were reviewed. RESULTS: We found insufficient data to perform a meta-analysis. However, there is evidence that swimmers have better expiratory flows and increased baseline lung volumes than non-athletes or non-swimmers. Although these features can result from changes in lung development following intense training over the years, the contribution of a genetic predisposition and positive selection cannot be totally excluded. CONCLUSION: Disentangling the participation of constitutional factors and years of hard training to explain the larger lung volumes of athletic swimmers is in favour of an adaptative response of the lungs to early swim training through modification of the pathway of lung development. There seems to be an optimal window of opportunity before the end of growth for these adaptational changes to occur. Precise mechanisms, and contribution of adaptative change on lung physiology, remain to be further studied.

Flow Volume Loop and Regional Ventilation Assessment Using Phase-Resolved Functional Lung (PREFUL) MRI: Comparison With 129 Xenon Ventilation MRI and Lung Function Testing.

BACKGROUND: Regional flow volume loop ventilation-weighted noncontrast-enhanced proton lung MRI in free breathing has emerged as a novel technique for assessment of regional lung ventilation, but has yet not been validated with 129 Xenon MRI (129 Xe-MRI), a direct visualization of ventilation in healthy volunteers, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) patients. PURPOSE: To compare regional ventilation and regional flow volume loops measured by noncontrast-enhanced ventilation-weighted phase-resolved functional lung MRI (PREFUL-MRI) with 129 Xe-MRI ventilation imaging and with lung function test parameters. STUDY TYPE: Retrospective study. POPULATION: Twenty patients with COPD, eight patients with CF, and six healthy volunteers. FIELD STRENGTH/SEQUENCE: PREFUL and 129 Xe-MRI gradient echo sequences were acquired at 1.5T. ASSESSMENT: Coronal slices of PREFUL-MRI (free breathing) and 129 Xe-MRI (single breath-hold) were acquired on the same day, matched by their ventrodorsal position and coregistered for evaluation. Ventilation defect percentage (VDP) was calculated based on regional ventilation (RV), regional flow volume loops (RFVL), or 129 Xe-MRI with two different threshold methods. A combined VDP was calculated for RV and RFVL. Additionally, lung function testing was performed (such as the forced expiratory volume in 1 second [FEV1 ]) was used. STATISTICAL TESTS: The obtained parameters were compared using Wilcoxon tests, correlated using Spearman's correlation coefficient (r), and agreement between PREFUL and 129 Xe-MRI parameters was assessed using Bland-Altman analysis and Dice coefficients. RESULTS: VDP measured by PREFUL and 129 Xe were significantly correlated with both thresholding techniques (r = 0.62-0.69, P < 0.05 for all) and with lung function test parameters. Combined RV and RFVL PREFUL defect maps correlated with lung function testing (eg, with FEV1 r = -0.87 P < 0.05), and showed better regional agreement to 129 Xe-MRI ventilation defects (Dice coefficient defect 0.413) with significantly higher VDP values (10.2 ± 27.3, P = 0.04) than either PREFUL defect map alone. DATA CONCLUSION: Combined RV and RFVL PREFUL defect maps likely increase sensitivity to mild airway obstruction with increased VDP values compared to 129 Xe-MRI, and correlate strongly with lung function test parameters. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Impact of unilateral diaphragm elevation on postoperative outcomes in bilateral lung transplantation - a retrospective single-center study.

This study evaluated the impact of unilateral diaphragm elevation following bilateral lung transplantation on postoperative course. Patient data for all lung transplantations performed at our institution between 01/2010 and 12/2019 were reviewed. Presence of right or left diaphragm elevation was retrospectively evaluated using serial chest X-rays performed while patients were standing and breathing spontaneously. Right elevation was defined by a > 40 mm difference between right and left diaphragmatic height. Left elevation was present if the left diaphragm was at the same height or higher than the right diaphragm. In total, 1093/1213 (90%) lung transplant recipients were included. Of these, 255 (23%) patients exhibited radiologic evidence of diaphragm elevation (right, 55%; left 45%; permanent, 62%). Postoperative course did not differ between groups. Forced expiratory volume in 1 second, forced vital capacity and total lung capacity were lower at 1-year follow-up in patients with permanent than in patients with transient or absent diaphragmatic elevation (P = 0.038, P < 0.001, P = 0.002, respectively). Graft survival did not differ between these groups (P = 0.597). Radiologic evidence of diaphragm elevation was found in 23% of our lung transplant recipients. While lung function tests were worse in patients with permanent elevation, diaphragm elevation did not have any relevant impact on outcomes.

Air Trapping Is Associated with Heterozygosity for Alpha-1 Antitrypsin Mutations in Patients with Asthma.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD. OBJECTIVES: The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the SERPINA1 gene coding for AAT versus asthmatic subjects without mutation. METHODS: We performed the quantitative analysis of the serum concentration of AAT in 600 outpatients affected by mild to moderate asthma from the University Hospital of Parma, Italy. Fifty-seven of them underwent the genetic analysis subsequently; they were subdivided into mutated and non-mutated subjects. All the mutated patients had a heterozygous genotype, except 1 (PI*SS). We assessed the lung function through a flow-sensing spirometer and the small airway parameters through an impulse oscillometry system. RESULTS: The values of forced vital capacity (% predicted) and those of the residual volume to total lung capacity ratio (%) were, respectively, lower and higher in patients mutated versus patients without mutation, showing a significantly greater air trapping (p = 0.014 and p = 0.017, respectively). Moreover, patients with mutation in comparison to patients without mutation showed lower forced expiratory volume in 3 s (% predicted) and forced expiratory volume in 6 s (L) spirometric values, reflecting a smaller airways contribution. CONCLUSIONS: In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes was associated with small airway dysfunction and with lung air trapping.

Factors Associated With Asthma Control in 121 Preschool Children.

BACKGROUND AND OBJECTIVES: Data on risk factors for uncontrolled asthma in preschool children are controversial. Objective: This study aims to explore the association between clinical and functional parameters and the lack of asthma control in preschool children. METHODS: Children aged 3-5 years with asthma and healthy controls were recruited. A questionnaire was used to identify potential risk factors for uncontrolled asthma, as defined by the Global INitiative for Asthma criteria. Lung function and bronchial reversibility were evaluated through impulse oscillometry and spirometry. Adjusted odds ratios were estimated based on multivariable generalized additive regression models. The discriminative ability of the models was measured by the area under the receiver operating characteristic curve (AUC). RESULTS: The study population comprised 121 children (107 with asthma and 14 healthy controls). Fifty-three patients (50%) had uncontrolled asthma. After adjustment, the variables associated with an increased risk of lack of control were as follows: "More than 3 flare-ups in the last 12 months", "Moderate to severe rhinitis", and "Relative variation in postbronchodilator FVC and FEV1". The AUC of the final models that included variation in FVC or FEV1 were 0.82 and 0.81, respectively. The R5-20, R5-20%, and AX z-score values of the healthy group were lower than those of children with asthma. CONCLUSION: In preschool children, clinical and functional parameters are associated with uncontrolled asthma. More studies are needed to confirm the usefulness of impulse oscillometry.

Functional Examination of the Upper and Lower Airways in Asthma and Respiratory Allergic Diseases: Considerations in the Post-SARS-CoV-2 Era.

Airway examination procedures can potentially transmit infectious diseases to patients and to the health care professionals who perform them via various mechanisms. The COVID-19 pandemic has halted most of the activity of the clinics and laboratories involved in assessment of lung and nasal function, and clear recommendations in this regard have been made. Today, we still do not know for sure what its consequences will be in the short or long term, since important gaps remain in our knowledge of aspects as fundamental as virus transmission mechanisms, pathophysiology, immune response, and diagnosis. In this review, we study the examination techniques used to assess patients with respiratory allergy, asthma, and associated diseases during this period and highlight their possible advantages and disadvantages. Therefore, we focus on exploring the entire upper and lower airways, from the perspective of the safety of both health professionals and patients and their specific characteristics. We also analyze the intrinsic value of these interventions in terms of diagnosis and patient management. The changing situation of COVID-19 may mean that some of the assertions presented in this review will have to be modified in the future. While we seek to ensure a consistently broad approach, some differences in operational details may apply owing to local regulations.

Quality of life was similar in children with congenital diaphragmatic hernia and oesophageal atresia and related to respiratory morbidity.

AIM: To assess quality of life (QoL) in children with congenital diaphragmatic hernia (CDH) and to compare it with oesophageal atresia (OA). METHODS: A cross-sectional study in CDH children (≥7 years) was conducted in Lille University Hospital, France, from January 2013 to April 2014. History, lung function (rest, exercise) and Pediatric Quality of Life Inventory questionnaires (PedsQoL 4.0) were collected. Data of OA children were previously published. RESULTS: Fifty-four CDH patients (male: 53%, median age: 11 years, IQR 9-14) were compared to 54 OA patients (male: 61%, median age: 13 years, IQR: 11-15). CDH children had significantly more frequent history of pneumonia (30% vs 13%), exercise limitation (54% vs 35%) and chest deformity (39% vs 11%); 46% had an obstructive pattern and 66% an abnormal cardiopulmonary exercise test. The median PedsQoL total score in children was 81 (IQR 73-90) in CDH and 81 (IQR 72-91) in OA (P = .8). In CDH, duration of neonatal oxygen therapy, hospitalisation for respiratory disease, exercise limitation, inhaled corticosteroids treatment, chest deformity, abnormal cardiopulmonary exercise test and lower forced expiratory volume in one second were significantly associated with lower QoL scores. CONCLUSION: PedsQoL scores remained satisfactory in CDH children with CDH, with no difference compared to OA. Patients with respiratory morbidity and lung function impairment, who displayed lower scores, should be identified in order to optimise their management in reference centres.

It Is Not Just the FEV1 That Matters, but the Personal Goals We Reach Along the Way: Qualitative, Multicenter, Prospective, Observational Study.

BACKGROUND: The COVID-19 pandemic has boosted the use of forced expiratory volume in 1 second (FEV1) telemonitoring in pediatric asthma, but a consensus on its most efficient and effective implementation is still lacking. To find answers, it is important to study how such an intervention is perceived, experienced, and used by both patients and health care professionals (HCPs). OBJECTIVE: The aim of this study was to provide perspectives on how FEV1 home monitoring should be used in pediatric asthma. METHODS: This is a qualitative, multicenter, prospective, observational study which included patients with asthma aged 6-16 and HCPs. Primary outcomes were results of 2 surveys that were sent to all participants at study start and after 3-4 months. Secondary outcomes consisted of FEV1 device usage during 4 months after receiving the FEV1 device. RESULTS: A total of 39 participants (26 patients and 13 HCPs) were included in this study. Survey response rates were 97% (38/39) at the start and 87% (34/39) at the end of the study. Both patients and HCPs were receptive toward online FEV1 home monitoring and found it contributive to asthma control, self-management, and disease perception. The main concerns were about reliability of the FEV1 device and validity of home-performed lung function maneuvers. FEV1 devices were used with a median frequency of 7.5 (IQR 3.3-25.5) during the 4-month study period. CONCLUSIONS: Patients and HCPs are receptive toward online FEV1 home monitoring. Frequency of measurements varied largely among individuals, yet perceived benefits remained similar. This emphasizes that online FEV1 home monitoring strategies should be used as a means to reach individual goals, rather than being a goal on their own.

Fraction of Exhaled Nitric Oxide Levels Are Elevated in People Living With Human Immunodeficiency Virus Compared to Uninfected Controls, Suggesting Increased Eosinophilic Airway Inflammation.

BACKGROUND: Increased risk of asthma and chronic obstructive pulmonary disease has been reported in people living with human immunodeficiency virus (PLWH). Fraction of exhaled nitric oxide (FeNO) is a marker of eosinophilic airway inflammation. We assessed FeNO levels in PLWH and matched uninfected controls and investigated whether human immunodeficiency virus (HIV) status is independently associated with elevated FeNO. METHODS: FeNO was quantified by NIOX Vero and pulmonary function was assessed by spirometry in 432 PLWH from the Copenhagen Comorbidity in HIV Infection Study and in 1618 age- and sex-matched uninfected controls from the Copenhagen General Population Study. Elevated FeNO was defined as ≥25 parts per billion. Associations between FeNO and HIV status were adjusted for known potential confounders. RESULTS: Mean age of PLWH was 50.7 (standard deviation [SD], 11.1) years and 97.4% received combination antiretroviral therapy. PLWH had higher FeNO than uninfected controls (median, 17.0 [interquartile range {IQR}, 11.0-26.0] vs 13.0 [IQR, 9.0-19.0]; P < .001). Also, PLWH had a higher prevalence of elevated FeNO than uninfected controls (27.5% vs 12.3%; P < .001). This association remained after adjusting for age, sex, height, smoking status, use of airway medication, blood eosinophils, and immunoglobulin E (adjusted OR [aOR], 3.56 [95% CI, 2.51-5.04]; P < .001). Elevated FeNO was associated with self-reported asthma (aOR, 2.65 [95% CI, 1.66-4.24]; P < .001) but not with airflow limitation (aOR, 1.07 [95% CI, .71-1.62]; P = .745). CONCLUSIONS: HIV status was independently associated with elevated FeNO, suggesting increased eosinophilic airway inflammation. The potential impact on chronic lung disease pathogenesis needs further investigation.

Pulmonary outcomes in adults with a history of Bronchopulmonary Dysplasia differ from patients with asthma.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a risk factor for respiratory disease in adulthood. Despite the differences in underlying pathology, patients with a history of BPD are often treated as asthmatics. We hypothesized that pulmonary outcomes and health-related quality of life (HRQoL) were different in adults born preterm with and without a history of BPD compared to asthmatics and healthy individuals. METHODS: We evaluated 96 young adults from the LUNAPRE cohort ( clinicaltrials.gov/ct2/show/NCT02923648 ), including 26 individuals born preterm with a history of BPD (BPD), 23 born preterm without BPD (preterm), 23 asthmatics and 24 healthy controls. Extensive lung function testing and HRQoL were assessed. RESULTS: The BPD group had more severe airway obstruction compared to the preterm-, (FEV1- 0.94 vs. 0.28 z-scores; p ≤ 0.001); asthmatic- (0.14 z-scores, p ≤ 0.01) and healthy groups (0.78 z-scores, p ≤ 0.001). Further, they had increased ventilation inhomogeneity compared to the preterm- (LCI 6.97 vs. 6.73, p ≤ 0.05), asthmatic- (6.75, p = 0.05) and healthy groups (6.50 p ≤ 0.001). Both preterm groups had lower DLCO compared to healthy controls (p ≤ 0.001 for both). HRQoL showed less physical but more psychological symptoms in the BPD group compared to asthmatics. CONCLUSIONS: Lung function impairment and HRQoL in adults with a history of BPD differed from that in asthmatics highlighting the need for objective assessment of lung health.

Comparison of quantitative regional perfusion-weighted phase resolved functional lung (PREFUL) MRI with dynamic gadolinium-enhanced regional pulmonary perfusion MRI in COPD patients.

BACKGROUND: Perfusion-weighted noncontrast-enhanced proton lung MRI during free breathing is maturing as a novel technique for assessment of regional lung perfusion, but has not yet been validated in chronic obstructive pulmonary disease (COPD) patients. PURPOSE: To compare pulmonary parenchymal perfusion assessed by noncontrast-enhanced perfusion-weighted phase-resolved functional lung (PREFUL)-MRI with lung perfusion determined with dynamic gadolinium-enhanced (DCE)-MRI and with lung function test parameters. STUDY TYPE: Prospective. POPULATION: A single-center subset of the COPD cohort "COPD and SYstemic consequenzes-COmorbidities NETwork" (COSYCONET). Forty-seven patients with COPD (median age 66 [57-70] years) were studied. FIELD STRENGTH/SEQUENCE: For PREFUL-MRI a spoiled gradient echo sequence and for DCE-MRI, a 3D time-resolved spoiled gradient echo sequence was used at 1.5T. ASSESSMENT: PREFUL-MRI coronal slices were acquired in free breathing. DCE-MRI was performed in breath-hold with administration of 0.025 mmol/kg bodyweight of gadobutrol i.v. at a rate of 4 ml/s and pulmonary blood flow (PBF) maps were calculated. Slices of PREFUL and DCE-MRI were matched by their ventrodorsal position and corresponding slices were coregistered for evaluation. Perfusion defect percentages (QDP) were calculated for both methods. STATISTICAL TESTS: The obtained parameters were correlated using Spearman's correlation coefficient (r) and Bland-Altman plot analysis. RESULTS: PREFUL-QDP showed an absolute and spatial agreement with PBF-QDP on a global (39.3 (31.8-45.5)% vs. 44.7 (35.4-50.0)% with a spatial overlap of 62.2 (57.2-67.2)%)) as well as on a lobar level and correlated with lung function test parameters (PREFUL-QDP vs. FEV1 , r = -0.75, P < 0.0001). There was a systematic overestimation of PREFUL-QDP compared with PBF-QDP, mainly in the lower lobes, resulting in an overall overestimation for the whole lung with a mean difference of 5% (95% confidence interval [CI]: 3.0%; 7.0%; STD 6.8%). DATA CONCLUSION: PREFUL-MRI is a promising noninvasive, radiation-free tool for quantification of regional perfusion in COPD patients. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1122-1132.

Comparison of quantitative regional ventilation-weighted fourier decomposition MRI with dynamic fluorinated gas washout MRI and lung function testing in COPD patients.

BACKGROUND: Ventilation-weighted Fourier decomposition-MRI (FD-MRI) has matured as a reliable technique for quantitative measures of regional lung ventilation in recent years, but has yet not been validated in COPD patients. PURPOSE/HYPOTHESIS: To compare regional fractional lung ventilation obtained by ventilation-weighted FD-MRI with dynamic fluorinated gas washout MRI (19 F-MRI) and lung function test parameters. STUDY TYPE: Prospective study. POPULATION: Twenty-seven patients with chronic obstructive pulmonary disease (COPD, median age 61 [54-67] years) were included. FIELD STRENGTH/SEQUENCE: For FD-MRI and for 19 F-MRI a spoiled gradient echo sequence was used at 1.5T. ASSESSMENT: FD-MRI coronal slices were acquired in free breathing. Dynamic 19 F-MRI was performed after inhalation of 25-30 L of a mixture of 79% fluorinated gas (C3 F8 ) and 21% oxygen via a closed face mask tubing using a dedicated coil tuned to 59.9 MHz. 19 F washout times in numbers of breaths (19 F-nbreaths ) as well as fractional ventilation maps for both methods (FD-FV, 19 F-FV) were calculated. Slices were matched using a landmark driven algorithm, and only corresponding slices with an overlap of >90% were coregistered for evaluation. STATISTICAL TESTS: The obtained parameters were correlated with each other using Spearman's correlation coefficient (r). RESULTS: FD-FV strongly correlated with 19 F-nbreaths on a global (r = -0.72, P < 0.0001) as well as on a lobar level and with lung function test parameters (FD-FV vs. FEV1, r = 0.76, P < 0.0001). There was a small systematic overestimation of FD-FV compared to 19 F-FV (mean difference -0.03 (95% confidence interval [CI]: -0.097; -0.045). DATA CONCLUSION: Regional ventilation-weighted Fourier decomposition-MRI is a promising noninvasive, radiation-free tool for quantification of regional ventilation in COPD patients. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1534-1541.