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Environmental Health : a Global Access... Jul 2018Air pollution has been found to adversely affect children's lung function. Forced expiratory volume in 1 s and forced vital capacity from spirometry have been studied...
BACKGROUND
Air pollution has been found to adversely affect children's lung function. Forced expiratory volume in 1 s and forced vital capacity from spirometry have been studied most frequently, but measurements of airway resistance may provide additional information. We assessed associations of long-term air pollution exposure with airway resistance.
METHODS
We measured airway resistance at age 8 with the interrupter resistance technique (R) in participants of the Dutch PIAMA birth cohort study. We linked R with estimated annual average air pollution concentrations [nitrogen oxides (NO, NO), PM absorbance ("soot"), and particulate matter < 2.5 μm (PM), < 10 μm (PM) and 2.5-10 μm (PM)] at the birth address and current home address (n = 983). Associations between air pollution exposure and interrupter resistance (R) were assessed using multiple linear regression adjusting for potential confounders.
RESULTS
We found that higher levels of NO at the current address were associated with higher R [adj. mean difference (95% confidence interval) per interquartile range increase in NO: 0.018 (0.001, 0.035) kPa·s·L]. Similar trends were observed for the other pollutants, except, PM. No association was found between R and exposure at the birth address.
CONCLUSIONS
Our results support the hypothesis that air pollution exposure is associated with a lower lung function in schoolchildren.
Topics: Air Pollutants; Air Pollution; Airway Resistance; Child; Cohort Studies; Humans; Netherlands; Nitrogen Oxides; Particulate Matter; Soot
PubMed: 30016982
DOI: 10.1186/s12940-018-0407-9 -
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 -
Laryngoscope Investigative... Dec 2017To assess breathing behaviors and perception of added respiratory loads in young compared to old individuals, and to determine whether aging affects the perception and...
OBJECTIVES
To assess breathing behaviors and perception of added respiratory loads in young compared to old individuals, and to determine whether aging affects the perception and response to changes in nasal airway resistance.
STUDY DESIGN
In a clinical study, 40 young (11-20 years) and 40 older (59-82 years) subjects were evaluated during rest breathing and during the application of added airway resistance loads.
METHODS
The pressure-flow technique was used to measure airflow rate (mL/s) and oral-nasal pressures (cmHO) to calculate nasal resistance (cmHO/L/s). To create calibrated resistance loads for the test conditions, we used a device modified from a precision iris diaphragm.
RESULTS
During rest breathing airflow rate was significantly lower for the younger group compared to older group. Using the loading device, 11-20-year-olds detected increased resistance at the level of 2.26 cmHO/L/s compared to 4.55 cmHO/L/s in 59-82-year-olds. In contrast to the younger group, mean airflow rate was higher during expiration than during inspiration among 59-82-year-olds except at rest breathing.
CONCLUSIONS
The data revealed that the perception and respiratory response to increased airway resistance changed with aging. Younger subjects were more sensitive to changes within the airway. In both groups, subjects responded to increased airway resistance by decreasing airflow rate. However, expiratory phase became more active than inspiratory phase only in the older group.
LEVEL OF EVIDENCE
N/A.
PubMed: 29299517
DOI: 10.1002/lio2.123 -
Lung Jun 2021Mouse models have become an indispensable tool in translational research of human airway disease and have provided much of our understanding of the pathogenesis of... (Review)
Review
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 (EF) 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 EF with the invasive assessment of lung resistance and dynamic compliance with a somewhat lower sensitivity of EF. The measurement of EF 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.
Topics: Airway Resistance; Animals; COVID-19; Disease Models, Animal; Lung; Mice; Plethysmography, Whole Body; Respiratory Function Tests; Respiratory Mechanics; SARS-CoV-2
PubMed: 34009429
DOI: 10.1007/s00408-021-00443-9 -
Annals of the American Thoracic Society Oct 2014Chest wall strapping (CWS) induces breathing at low lung volumes. Mild to moderate obesity can lead to similar changes in lung volumes, due to chest wall and abdominal... (Review)
Review
Chest wall strapping (CWS) induces breathing at low lung volumes. Mild to moderate obesity can lead to similar changes in lung volumes, due to chest wall and abdominal restriction. Chest wall strapping is also conceptually similar to a mismatch between significantly oversized donor lungs transplanted into a recipient with a smaller chest cavity. Chest wall strapping increases lung elastic recoil, reduces pulmonary compliance, and substantially increases maximal expiratory flows. The interactions between elastic properties of the lung parenchyma and small airways are critical for pulmonary function. Chest wall strapping lowers residual volume and closing volume, likely from the interdependence between increased elastic recoil and airways, leading to greater radial distending forces on small airways and small airway dilation. Chronic obstructive pulmonary disease (COPD) and chronic rejection of the transplanted lung, bronchiolitis obliterans syndrome (BOS), are primarily diseases of the small airways, and are characterized by progressive obstruction and subsequent loss of small airways. In COPD, higher body mass index (BMI) (conceptually like being more tightly strapped) is associated with lower lung volumes, increased airway conductance, and lower risk of progression to emphysema or death. Likewise, in lung transplantation, oversized donor lungs have been linked to higher expiratory airflows, lower risk of bronchiolitis obliterans syndrome, and improved survival. This article reviews the physiology of chest wall strapping and explores how it could enhance the understanding or even the treatment of small airway diseases, such as COPD and bronchiolitis obliterans syndrome.
Topics: Airway Resistance; Bronchiolitis Obliterans; Humans; Lung Volume Measurements; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation
PubMed: 25172621
DOI: 10.1513/AnnalsATS.201312-465OI -
American Journal of Physiology. Lung... Sep 2021Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory...
Store-operated calcium entry (SOCE) is involved in the pathogenesis of airway inflammation and remodeling in asthma. Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs). Balb/c mice were sensitized and challenged with ovalbumin to establish the asthma mice models. Mice were transfected with lentivirus, which expressed the gene + GFP (green fluorescence protein) or the negative control gene + GFP. Airway resistance was measured with the animal pulmonary function system. Airway inflammation and remodeling were evaluated via histological staining. In vitro cultured hASMCs were transfected with scrambled small interfering RNA (siRNA) or SARAF-specific siRNA, respectively. The proliferation, migration rate, hypertrophy, and SOCE activity of hASMCs were examined with Cell Counting Kit-8, wound healing test, bright field imaging, and Ca fluorescence imaging, respectively. SARAF expression was measured by quantitative real-time PCR. Asthma mice models showed decreased SARAF mRNA expression in the lungs. SARAF overexpression attenuated airway inflammation, resistance, and also remodeling. Downregulation of SARAF expression with siRNA promoted the proliferation, migration, hypertrophy, and SOCE activity in hASMCs. SARAF plays a protective role against airway inflammation and remodeling in asthma mice models by blunting SOCE; SARAF may also be a functional regulating factor of hASMCs.
Topics: Airway Remodeling; Airway Resistance; Animals; Asthma; Calcium-Binding Proteins; Female; Gene Expression Regulation; Humans; Inflammation; Lung; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Myocytes, Smooth Muscle
PubMed: 34231388
DOI: 10.1152/ajplung.00079.2020 -
Experimental Physiology Feb 2019What is the central question of this study? The aim of this study was to evaluate artesunate for its use as a bronchodilator in asthma treatment. What is the main...
NEW FINDINGS
What is the central question of this study? The aim of this study was to evaluate artesunate for its use as a bronchodilator in asthma treatment. What is the main finding and its importance? We found that artesunate reduces airway resistance in both normal and ovalbumin-treated Balb/c mice in vivo. Artesunate reduces traction force while inducing Ca influx into cultured airway smooth muscle cells in vitro, most probably via the bitter taste receptor. These findings provide important evidence at both animal and cellular levels that artesunate might potentially be used as a bronchodilator for treating obstructive airway diseases, such as asthma.
ABSTRACT
Following the surprising discovery that bitter taste receptors (TAS2Rs) expressed in the lung and can be stimulated to relax airway smooth muscle cells (ASMCs), there is great interest in searching for a bitter taste receptor agonist as a new bronchodilator for asthma therapy. Among the great many other natural bitter substances, artesunate is of special interest to be evaluated for this purpose because of its pharmacological value as a derivative from the well-known anti-malarial, artemisinin. Therefore, in this study we treated either normal or ovalbumin (OVA)-induced asthmatic Balb/c mice in vivo with artesunate (30, 60 or 120 μg) via aerosol inhalation. Subsequently, we measured the airway resistance of the mice in the presence or absence of artesunate. In addition, we treated either mouse or human ASMCs cultured in vitro with artesunate (0.25-2.0 mM) and then measured the traction force and [Ca ] flux of the cells in the presence or absence of artesunate. The results demonstrate that artesunate attenuated airway resistance in a dose-dependent manner in both the normal and the OVA-treated mice, but more potently in the latter. The in vivo efficacy of artesunate at 120 μg was comparable to that of the conventional bronchodilator, salbutamol, at 3 μg in terms of the reduction in airway resistance. Artesunate also reduced traction force and induced an increase in [Ca ] in the cultured ASMCs, which was mediated, at least in part, by TAS2R signalling in the human ASMCs. These results together suggest that artesunate might potentially be a cheap and safe bronchodilator to complement the current therapy of asthma.
Topics: Airway Resistance; Animals; Artemisinins; Artesunate; Asthma; Bronchoconstriction; Bronchodilator Agents; Calcium; Calcium Signaling; Female; Lung; Mice; Mice, Inbred BALB C; Muscle Relaxation; Muscle, Smooth; Myocytes, Smooth Muscle; Receptors, Calcium-Sensing; Receptors, G-Protein-Coupled; Taste
PubMed: 30379382
DOI: 10.1113/EP086824 -
Journal of Applied Physiology... May 2021We investigated the effects of heliox administration (80% helium in O) on tidal inspiratory flow limitation (tIFL) occurring in supine anesthetized spontaneously...
We investigated the effects of heliox administration (80% helium in O) on tidal inspiratory flow limitation (tIFL) occurring in supine anesthetized spontaneously breathing rabbits, regarded as an animal model of obstructive apnea-hypopnea syndrome. 22 rabbits were instrumented to record oro-nasal mask flow, airway opening, tracheal and esophageal pressures, and diaphragm and genioglossus electromyographic activities while breathing either room air or heliox, and, in 12 rabbits, also during the application of continuous positive airway pressure (CPAP; 6 cmHO). For the group, heliox increased peak inspiratory flow, ventilation (18 ± 11%), peak inspiratory tracheal and dynamic transpulmonary pressures, but in no animal eliminated tIFL, as instead CPAP did in all. Muscle activities were unaffected by heliox. In the presence of IFL the increase in flow with heliox (ΔV̇ifl) varied markedly among rabbits (2 to 49%), allowing the distinction between responders and non-responders. None of the baseline variables discriminated responders and non-responders. However, fitting the Rohrer equation ( = + V̇) to the tracheal pressure-flow relationship over the first 0.1 s of inspiration while breathing air allowed such discrimination on the basis of larger in responders (0.005 ± 0.002 versus 0.002 ± 0.001 cmHO·s·ml; < 0.001), suggesting a corresponding difference in the relative contribution of laminar and turbulent flow. The differences in ΔV̇ifl between responders and non-responders were simulated by modeling the collapsible segment of the upper airways as a non-linear resistor and varying its pressure-volume curve, length, and diameter, thus showing the importance of mechanical and geometrical factors in determining the response to heliox in the presence of tIFL. In an obstructive sleep apnea rabbit model, heliox never abolishes tidal inspiratory flow limitation (IFL), but increases inspiratory flow and tidal volume, substantially in some and nearly nil in other animals. Positive response to heliox cannot be predicted on the basis of breathing pattern characteristics or upper airway resistance that preceded IFL onset, but is related to the mechanical and geometrical features of upper airway collapsible segment, as indicated by model simulation.
Topics: Airway Resistance; Animals; Helium; Oxygen; Rabbits; Tidal Volume
PubMed: 33411637
DOI: 10.1152/japplphysiol.00830.2020 -
Clinics in Chest Medicine Mar 2019Airway smooth muscle is the primary cell mediating bronchomotor tone. The milieu created in the asthmatic lung modulates airway smooth muscle contractility and... (Review)
Review
Airway smooth muscle is the primary cell mediating bronchomotor tone. The milieu created in the asthmatic lung modulates airway smooth muscle contractility and relaxation. Experimental findings suggest intrinsic abnormalities in airway smooth muscle derived from patients with asthma in comparison with airway smooth muscle from those without asthma. These changes to excitation-contraction pathways may underlie airway hyperresponsiveness and increased airway resistance associated with asthma.
Topics: Airway Resistance; Asthma; Bronchoconstriction; Bronchodilator Agents; Humans; Muscle, Smooth
PubMed: 30691716
DOI: 10.1016/j.ccm.2018.10.003 -
Turkish Thoracic Journal Oct 2015The measurement of lung function by spirometry is routinely used to monitor and adequately treat children with asthma. The assessment and evaluation of lung function in... (Review)
Review
The measurement of lung function by spirometry is routinely used to monitor and adequately treat children with asthma. The assessment and evaluation of lung function in children aged 3-5 years has been neglected for a long time because of the difficulty to perform forced expiratory maneuvers. However, the use of techniques such as the interrupter technique and the forced oscillation technique, which only require passive collaboration and where the only request to the child is to breathe at tidal volume, has overcome this limitation. Other techniques such as the measurement of specific airway resistance by plethysmography or the measurement of the lung clearance index using the multiple-breath washout might be helpful in this regard, although these techniques are less standardized in preschool children.
PubMed: 29404101
DOI: 10.5152/ttd.2015.5038