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Pediatric Pulmonology Nov 2023Mechanisms underlying lung dysfunction after preterm birth are poorly understood. Studying phenotypes of prematurity-associated lung disease may aid understanding of...
INTRODUCTION
Mechanisms underlying lung dysfunction after preterm birth are poorly understood. Studying phenotypes of prematurity-associated lung disease may aid understanding of underlying mechanisms. Preterm-born children with and without lung dysfunction and term controls were assessed using oscillometry before and after exercise, and after postexercise bronchodilation.
METHODS
Preterm-born children, born at gestation of 34 weeks or less, were classified into those with prematurity-associated obstructive lung disease (POLD; FEV < LLN, FEV /FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (pPRISm; FEV < LLN, FEV /FVC ≥ LLN) and compared to preterm (FEV ≥ LLN) and term controls (%predicted FEV > 90%). All children underwent cardiopulmonary exercise, and oscillometry assessment at baseline, postexercise, and after postexercise bronchodilator administration.
RESULTS
From 241 participants aged 7-12 years, complete data were available from 179: 15 children with POLD and 11 with pPRISm were compared with 93 preterm and 60 term controls. POLD group, when compared to both control groups, had impaired impedance, greater resistance, more negative (greater magnitude) reactance at low frequencies, and also had decreased compliance. pPRISm group demonstrated impaired reactance and compliance compared to term controls. No differences were noted between the preterm and term controls. Exercise had little impact on oscillometry values, but children with POLD had greatest improvements after postexercise bronchodilator administration, with decreased resistance and decreased magnitude of reactance, particularly at low frequencies.
CONCLUSION
Preterm-born children with obstructive airway disease had the greatest oscillometry impairments and the largest improvements after postexercise bronchodilator compared to control groups. Oscillometry can potentially be used to identify preterm-born children with lung disease to institute treatment.
Topics: Child; Female; Humans; Infant, Newborn; Bronchodilator Agents; Oscillometry; Forced Expiratory Volume; Premature Birth; Lung; Lung Diseases; Lung Diseases, Obstructive; Spirometry; Infant, Newborn, Diseases
PubMed: 37701982
DOI: 10.1002/ppul.26658 -
Respiratory Research Mar 2022Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify Tc-hydroxy methylene diphosphonate (HMDP)...
BACKGROUND
Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify Tc-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 Tc-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 Tc-HMDP retention and pulmonary function parameters shown statistically significant correlations with total lung volume (% predicted), lung reactance (X 5 Hz) and peak VO, 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 Tc-HMDP may occur in patients with cardiac ATTRv amyloidosis, which can elicit deleterious effects on patient's lung function and aerobic capacity.
Topics: Amyloidosis; Humans; Lung; Prealbumin; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Medronate
PubMed: 35346209
DOI: 10.1186/s12931-022-01995-x -
Chest Apr 2023The purpose of this study was to investigate physiological phenotypes of asthma in obesity.
BACKGROUND
The purpose of this study was to investigate physiological phenotypes of asthma in obesity.
RESEARCH QUESTION
Do physiological responses during bronchoconstriction distinguish different groups of asthma in people with obesity, and also differentiate from responses simply related to obesity?
STUDY DESIGN AND METHODS
Cross-sectional study of people with obesity (31 with asthma and 22 without lung disease). Participants underwent methacholine challenge testing with measurement of spirometry and respiratory system impedance by oscillometry.
RESULTS
Participants had class III obesity (BMI, 46.7 ± 6.6 kg/m in control subjects and 47.2 ± 8.2 kg/m in people with asthma). Most participants had significant changes in peripheral airway impedance in response to methacholine: in control subjects, resistance at 5 Hz measured by oscillometry increased by 45% ± 27% and area under the reactance curve (AX) by 268% ± 236% in response to 16 mg/mL methacholine; in people with asthma, resistance at 5 Hz measured by oscillometry increased by 52% ± 38% and AX by 361% ± 295% in response to provocation concentration producing a 20% fall in FEV dose of methacholine. These responses suggest that obesity predisposes to peripheral airway reactivity. Two distinct groups of asthma emerged based on respiratory system impedance: one with lower reactance (baseline AX, 11.8; interquartile range, 9.9-23.4 cm HO/L) and more concordant bronchoconstriction in central and peripheral airways; the other with high reactance (baseline AX, 46.7; interquartile range, 23.2-53.7 cm HO/L) and discordant bronchoconstriction responses in central and peripheral airways. The high reactance asthma group included only women, and reported significantly more gastroesophageal reflux disease, worse chest tightness, more wheeze, and more asthma exacerbations than the low reactance group.
INTERPRETATION
Peripheral airway reactivity detected by oscillometry is common in obese control subjects and obese people with asthma. There is a subgroup of obese asthma characterized by significant peripheral airway dysfunction by oscillometry out of proportion to spirometric airway dysfunction. This peripheral dysfunction represents clinically significant respiratory disease not readily assessed by spirometry.
Topics: Female; Humans; Methacholine Chloride; Cross-Sectional Studies; Asthma; Respiratory System; Spirometry; Bronchial Provocation Tests; Obesity; Airway Resistance; Forced Expiratory Volume
PubMed: 36610669
DOI: 10.1016/j.chest.2022.12.030 -
Scientific Reports Aug 2022This descriptive case series retrospectively reviewed medical records from thirty-one previously healthy, war-fighting veterans who self-reported exposure to airborne...
This descriptive case series retrospectively reviewed medical records from thirty-one previously healthy, war-fighting veterans who self-reported exposure to airborne hazards while serving in Iraq and Afghanistan between 2003 and the present. They all noted new-onset dyspnea, which began during deployment or as a military contractor. Twenty-one subjects underwent non-invasive pulmonary diagnostic testing, including maximum expiratory pressure (MEP) and impulse oscillometry (IOS). In addition, five soldiers received a lung biopsy; tissue results were compared to a previously published sample from a soldier in our Iraq Afghanistan War Lung Injury database and others in our database with similar exposures, including burn pits. We also reviewed civilian control samples (5) from the Stony Brook University database. Military personnel were referred to our International Center of Excellence in Deployment Health and Medical Geosciences, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell under the auspices of Northwell IRB: 17-0140-FIMR Feinstein Institution for Medical Research "Clinicopathologic characteristics of Iraq Afghanistan War Lung Injury." We retrospectively examined medical records, including exposure data, radiologic imaging, and non-invasive pulmonary function testing (MGC Diagnostic Platinum Elite Plethysmograph) using the American Thoracic Society (ATS) standard interpretation based on Morgan et al., and for a limited cohort, biopsy data. Lung tissue, when available, was examined for carbonaceous particles, polycyclic aromatic hydrocarbons (Raman spectroscopy), metals, titanium connected to iron (Brookhaven National Laboratory, National Synchrotron Light Source II, Beamline 5-ID), oxidized metals, combustion temperature, inflammatory cell accumulation and fibrosis, neutrophil extracellular traps, Sirius red, Prussian Blue, as well as polarizable crystals/particulate matter/dust. Among twenty-one previously healthy, deployable soldiers with non-invasive pulmonary diagnostic tests, post-deployment, all had severely decreased MEP values, averaging 42% predicted. These same patients concurrently demonstrated abnormal airways reactance (X5Hz) and peripheral/distal airways resistance (D5-D20%) via IOS, averaging - 1369% and 23% predicted, respectively. These tests support the concept of airways hyperresponsiveness and distal airways narrowing, respectively. Among the five soldiers biopsied, all had constrictive bronchiolitis. We detected the presence of polycyclic aromatic hydrocarbons (PAH)-which are products of incomplete combustion-in the lung tissue of all five warfighters. All also had detectable titanium and iron in the lungs. Metals were all oxidized, supporting the concept of inhaling burned metals. Combustion temperature was consistent with that of burned petrol rather than higher temperatures noted with cigarettes. All were nonsmokers. Neutrophil extracellular traps were reported in two biopsies. Compared to our prior biopsies in our Middle East deployment database, these histopathologic results are similar, since all database biopsies have constrictive bronchiolitis, one has lung fibrosis with titanium bound to iron in fixed mathematical ratios of 1:7 and demonstrated polarizable crystals. These results, particularly constrictive bronchiolitis and polarizable crystals, support the prior data of King et al. (N. Engl. J. Med. 365:222-230, 2011) Soldiers in this cohort deployed to Iraq and Afghanistan since 2003, with exposure to airborne hazards, including sandstorms, burn pits, and improvised explosive devices, are at high risk for developing chronic clinical respiratory problems, including: (1) reduction in respiratory muscle strength; (2) airways hyperresponsiveness; and (3) distal airway narrowing, which may be associated with histopathologic evidence of lung damage, reflecting inhalation of burned particles from burn pits along with particulate matter/dust. Non-invasive pulmonary diagnostic tests are a predictor of burn pit-induced lung injury.
Topics: Afghan Campaign 2001-; Afghanistan; Bronchiolitis Obliterans; Dust; Humans; Incineration; Iraq; Iraq War, 2003-2011; Iron; Lung; Lung Injury; Particulate Matter; Polycyclic Aromatic Hydrocarbons; Retrospective Studies; Titanium; United States
PubMed: 36038588
DOI: 10.1038/s41598-022-18252-2 -
ERJ Open Research Apr 2022Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with COPD, suggesting a role in disease pathogenesis. Sulfatase modifying factor...
Single nucleotide polymorphisms (SNPs) in various genes have been shown to associate with COPD, suggesting a role in disease pathogenesis. Sulfatase modifying factor (SUMF1) is a key modifier in connective tissue remodelling, and we have shown previously that several SNPs in are associated with COPD. The aim of this study was to investigate the association between SNPs and advanced lung function characteristics. Never-, former and current smokers with (n=154) or without (n=405) COPD were genotyped for 21 SNPs in and underwent spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide ( ) measurement and impulse oscillometry. Four SNPs (rs793391, rs12634248, rs2819590 and rs304092) showed a significantly decreased odds ratio of having COPD when heterozygous for the variance allele, together with a lower forced expiratory volume in 1 s (FEV) and FEV/forced vital capacity (FVC) ratio and an impaired peripheral resistance and reactance. Moreover, individuals homozygous for the variance allele of rs3864051 exhibited a strong association to COPD, a lower FEV/FVC, FEV and , and an impaired peripheral resistance and reactance. Other SNPs (rs4685744, rs2819562, rs2819561 and rs11915920) were instead associated with impaired lung volumes and exhibited a lower FVC, total lung capacity and alveolar volume, in individuals having the variance allele. Several SNPs in the gene are shown to be associated with COPD and impaired lung function. These genetic variants of may cause a deficient sulfation balance in the extracellular matrix of the lung tissue, thereby contributing to the development of COPD.
PubMed: 35586453
DOI: 10.1183/23120541.00668-2021 -
Physiological Reports Feb 2022Navy divers tend to have large lungs and low expiratory flow rates in the terminal portion of a spirogram. We examined Finnish Navy divers for the presence of air...
Navy divers tend to have large lungs and low expiratory flow rates in the terminal portion of a spirogram. We examined Finnish Navy divers for the presence of air trapping, airway obstruction, and functional airway compression, and their association with lung volumes. Divers (n = 57) and non-diving men (n = 10) underwent a variety of pulmonary function tests. The amount of trapped air was calculated as the subtraction of the total lung capacity (TLC) measured in a single-breath helium dilution test from the TLC in body plethysmography (TLCb). Mean vital capacity (VC) was 6.4 L in the divers versus 5.8 L in the controls (p = 0.006) and TLCb 8.9 L in the divers versus 8.1 L in the controls (p = 0.002). No difference existed between them in the amount of trapped air. However, we found break points in a linear regression model (Davies test) between trapped air and several pulmonary parameters. Those individuals above the break points had lower ratio of forced expiratory volume in first second to forced vital capacity, lower resistance of airways, and higher reactance than those below the break points. In conclusion, navy divers had larger lungs than controls. Large lung volumes (VC >7.31 L or >122% of predicted value) were associated with air trapping. Furthermore, large volumes of air trapping (>1.1 L) were associated with increased residual volume (RV) and RV/TLCb. Despite no concurrent obstruction, functional airway compression, or reduced diffusing capacity, this slowly ventilated trapped air might remain disadvantageous for divers.
Topics: Forced Expiratory Volume; Humans; Lung; Male; Respiratory Function Tests; Total Lung Capacity; Vital Capacity
PubMed: 35212176
DOI: 10.14814/phy2.15153 -
Frontiers in Physiology 2022Obesity impairs lung function and mechanics and leads to low-grade inflammation, but the effects of combined physical exercise (CPE) on that are unknown. We...
Obesity impairs lung function and mechanics and leads to low-grade inflammation, but the effects of combined physical exercise (CPE) on that are unknown. We investigated the effects of 12 weeks of combined physical exercise (aerobic + resistance training), in non-obese ( = 12), overweight ( = 17), and obese grade I ( = 11) women. Lung function and lung mechanics were evaluated. The systemic immune response was evaluated by whole blood analysis and biomarker measurements, while pulmonary fibrotic biomarkers were evaluated in the breath condensate. CPE improved forced vital capacity (FVC) % ( < 0.001) and peak expiratory flow (PEF) % ( < 0.0003) in the obese group; resistance of the respiratory system (R5Hz) in non-obese ( < 0.0099), overweight ( < 0.0005), and obese ( < 0.0001) groups; resistance of proximal airways (R20Hz) in non-obese ( < 0.01), overweight ( < 0.0009), and obese ( < 0.0001) groups; resistance of distal airways (R5Hz-R20Hz) in non-obese ( < 0.01), overweight ( < 0.0012), and obese ( < 0.0001) groups; reactance of the respiratory system (X5Hz) in non-obese ( < 0.01), overweight ( < 0.0006), and obese ( < 0.0005) groups; impedance of the respiratory system (Z5Hz) in non-obese ( < 0.0099), overweight ( < 0.0005), and obese ( < 0.0001) groups; central resistance (RCentral) in non-obese ( < 0.01), overweight ( < 0.001), and obese ( < 0.0003) groups; and the peripheral resistance (RPeripheral) in non-obese ( < 0.03), overweight ( < 0.001), and obese ( < 0.0002) groups. CPE reduced the pro-fibrotic IGF-1 levels in BC in overweight ( < 0.0094) and obese groups ( < 0.0001) and increased anti-fibrotic Klotho levels in BC in obese ( < 0.0001) groups, and reduced levels of exhaled nitric oxide in overweight ( < 0.03) and obese ( < 0.0001) groups. CPE improves lung function, mechanics, and pulmonary immune response in overweight and obese grade I women by increasing anti-fibrotic protein Klotho and reducing pro-fibrotic IGF-1.
PubMed: 36160852
DOI: 10.3389/fphys.2022.946402 -
The European Respiratory Journal Mar 2023Small airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of...
BACKGROUND
Small airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of the Small Airways Dysfunction Tool (SADT) questionnaire, basic patient characteristics and respiratory tests available depending on the clinical setting to predict SAD in asthma.
METHODS
This study was based on the data of the multinational ATLANTIS (Assessment of Small Airways Involvement in Asthma) study including the earlier developed SADT questionnaire. Key SADT items together with clinical information were now used to build logistic regression models to predict SAD group (less likely or more likely to have SAD). Diagnostic ability of the models was expressed as area under the receiver operating characteristic curve (AUC) and positive likelihood ratio (LR+).
RESULTS
SADT item 8, "I sometimes wheeze when I am sitting or lying quietly", and the patient characteristics age, age at asthma diagnosis and body mass index could reasonably well detect SAD (AUC 0.74, LR+ 2.3). The diagnostic ability increased by adding spirometry (percentage predicted forced expiratory volume in 1 s: AUC 0.87, LR+ 5.0) and oscillometry (resistance difference between 5 and 20 Hz and reactance area: AUC 0.96, LR+ 12.8).
CONCLUSIONS
If access to respiratory tests is limited ( primary care in many countries), patients with SAD could reasonably well be identified by asking about wheezing at rest and a few patient characteristics. In (advanced) hospital settings patients with SAD could be identified with considerably higher accuracy using spirometry and oscillometry.
Topics: Humans; Asthma; Respiratory Function Tests; Spirometry; Forced Expiratory Volume; ROC Curve
PubMed: 36517179
DOI: 10.1183/13993003.00558-2022 -
Temporal changes in pulmonary gas exchange efficiency when breath-hold diving below residual volume.Experimental Physiology Apr 2021What is the central question of this study? How does deep breath-hold diving impact cardiopulmonary function, both acutely and over the subsequent 2.5 hours post-dive?...
NEW FINDINGS
What is the central question of this study? How does deep breath-hold diving impact cardiopulmonary function, both acutely and over the subsequent 2.5 hours post-dive? What is the main finding and its importance? Breath-hold diving, to depths below residual volume, is associated with acute impairments in pulmonary gas exchange, which typically resolve within 2.5 hours. These data provide new insight into the behaviour of the lungs and pulmonary vasculature following deep diving.
ABSTRACT
Breath-hold diving involves highly integrative and extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure. Over two diving training camps (Study 1 and 2), 25 breath-hold divers (recreational to world-champion) performed 66 dives to 57 ± 20 m (range: 18-117 m). Using the deepest dive from each diver, temporal changes in cardiopulmonary function were assessed using non-invasive pulmonary gas exchange (indexed via the O deficit), ultrasound B-line scores, lung compliance and pulmonary haemodynamics at baseline and following the dive. Hydrostatically induced lung compression was quantified in Study 2, using spirometry and lung volume measurement, enabling each dive to be categorized by its residual volume (RV)-equivalent depth. From both studies, pulmonary gas exchange inefficiency - defined as an increase in O deficit - was related to the depth of the dive (r = 0.345; P < 0.001), with dives associated with lung squeeze symptoms exhibiting the greatest deficits. In Study 1, although B-lines doubled from baseline (P = 0.027), cardiac output and pulmonary artery systolic pressure were unchanged post-dive. In Study 2, dives with lung compression to ≤RV had higher O deficits at 9 min, compared to dives that did not exceed RV (24 ± 25 vs. 5 ± 8 mmHg; P = 0.021). The physiological significance of a small increase in estimated lung compliance post-dive (via decreased and increased/unaltered airway resistance and reactance, respectively) remains equivocal. Following deep dives, the current study highlights an integrated link between hydrostatically induced lung compression and transient impairments in pulmonary gas exchange efficiency.
Topics: Breath Holding; Cardiac Output; Pulmonary Gas Exchange; Residual Volume; Spirometry
PubMed: 33559974
DOI: 10.1113/EP089176 -
Scientific Reports Nov 2022The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have...
The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have received intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP), this study included 118 school-aged children who were grouped into three groups: full-term control children (group 1), preterm children who had not received IVB treatment (group 2) and preterm children with ROP who had received IVB treatment (group 3). Pulmonary function was measured by spirometry and impulse oscillometry. Pulmonary function was significantly better in group 1 than in groups 2 and 3 (all p < 0.05 in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV), forced expiratory flow between 25 and 75% of FVC (FEF), and respiratory resistance at 5 Hz and difference between respiratory resistance at 5 and 20 Hz (R5-R20). There were no statistically significant differences between group 2 and group 3 in all pulmonary function parameters, including FVC, FEV, ratio of FEV to FVC, FEF, R5, R20, R5-R20, and respiratory reactance at 5 Hz. In conclusion, our study revealed that preterm infants receiving IVB for ROP had comparable pulmonary function at school age to their preterm peers who had not received IVB treatment.
Topics: Infant; Child; Humans; Infant, Newborn; Bevacizumab; Retinopathy of Prematurity; Intravitreal Injections; Infant, Premature; Forced Expiratory Volume; Lung
PubMed: 36335152
DOI: 10.1038/s41598-022-22338-2