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The Journal of Allergy and Clinical... Nov 2023Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma...
BACKGROUND
Exposure to certain agents in the workplace can trigger occupational asthma or work-exacerbated asthma, both of which come under the heading of work-related asthma (WRA). Understanding the burden that WRA represents can help in the management of these patients.
OBJECTIVE
To assess the influence of occupation on asthma in real life and analyze the characteristics of patients with WRA included in an asthma cohort.
METHODS
This was a prospective multicenter study of a cohort of consecutive patients with asthma. A standardized clinical history was completed. Patients were classified as having WRA or non-WRA. All patients underwent respiratory function tests, FeNO test, and methacholine challenge (methacholine concentration that causes a 20% drop in FEV) at the beginning of the study. They were classified into two groups, depending on their employment status: employed (group 1) or unemployed (group 2).
RESULTS
Of the 480 patients included in the cohort, 82 (17%) received the diagnosis of WRA. Fifty-seven patients (70%) were still working. Mean age (SD) was 46 (10.69) years in group 1 and 57 (9.91) years in group 2 (P < .0001). Significant differences were observed in adherence to treatment (64.9% in group 1 vs 88% in group 2; P = .0354) and in severe asthma exacerbations (35.7% in group 1 vs 0% in group 2; P = .0172). No significant differences were observed in the rest of the variables analyzed.
CONCLUSIONS
The burden of WRA in specialized asthma units is not negligible. The absence of differences in the severity of asthma, the treatment administered, alterations in lung function, and the number of exacerbations in those working versus not working may support the idea that advice regarding changing jobs should be customized for individual patients.
Topics: Humans; Middle Aged; Asthma, Occupational; Bronchial Provocation Tests; Methacholine Chloride; Occupational Diseases; Occupational Exposure; Prospective Studies; Adult
PubMed: 37391017
DOI: 10.1016/j.jaip.2023.06.040 -
Toxicology and Applied Pharmacology Dec 2020Hydraulic fracturing creates fissures in subterranean rock to increase the flow and retrieval of natural gas. Sand ("proppant") in fracking fluid injected into the well...
Hydraulic fracturing creates fissures in subterranean rock to increase the flow and retrieval of natural gas. Sand ("proppant") in fracking fluid injected into the well bore maintains fissure patency. Fracking sand dust (FSD) is generated during manipulation of sand to prepare the fracking fluid. Containing respirable crystalline silica, FSD could pose hazards similar to those found in work sites where silica inhalation induces lung disease such as silicosis. This study was performed to evaluate the possible toxic effects following inhalation of a FSD (FSD 8) in the lung and airways. Rats were exposed (6 h/d × 4 d) to 10 or 30 mg/m of a FSD collected at a gas well, and measurements were performed 1, 7, 27 and, in one series of experiments, 90 d post-exposure. The following ventilatory and non-ventilatory parameters were measured in vivo and/or in vitro: 1) lung mechanics (respiratory system resistance and elastance, tissue damping, tissue elastance, Newtonian resistance and hysteresivity); 2) airway reactivity to inhaled methacholine (MCh); airway epithelium integrity (isolated, perfused trachea); airway efferent motor nerve activity (electric field stimulation in vitro); airway smooth muscle contractility; ion transport in intact and cultured epithelium; airway effector and sensory nerves; tracheal particle deposition; and neurogenic inflammation/vascular permeability. FSD 8 was without large effect on most parameters, and was not pro-inflammatory, as judged histologically and in cultured epithelial cells, but increased reactivity to inhaled MCh at some post-exposure time points and affected Na transport in airway epithelial cells.
Topics: Administration, Inhalation; Animals; Dust; Epithelial Cells; Hydraulic Fracking; Inhalation Exposure; Lung; Male; Methacholine Chloride; Occupational Exposure; Rats; Rats, Sprague-Dawley; Respiratory Mucosa; Sand; Silicon Dioxide; Trachea
PubMed: 33068619
DOI: 10.1016/j.taap.2020.115284 -
Iranian Journal of Allergy, Asthma, and... Feb 2019Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on...
Epidemiological and clinical studies have demonstrated a close association between obesity and asthma. The current study investigated the effect of high-fat diet on tracheal responsiveness to methacholine and insulin resistance in ovalbumin (OVA) sensitized male and female rats. The rats were divided into eight groups (n=6 per group): female with the normal diet (F+ND), male with the normal diet (M+ND), female OVA-sensitized with the normal diet (F+SND), male OVA-sensitized with the normal diet (M+SND), female with high-fat diet (F+HFD), male with high-fat diet (M+HFD), female OVA-sensitized with high-fat diet (F+SHFD), and male OVA-sensitized with high-fat diet (M+SHFD). All rats were fed for 8 weeks with high-fat diet or standard pelts, and for another 4 weeks, they were sensitized with OVA or saline. At the end of the study, the tracheal responsiveness to methacholine, serum insulin, and blood glucose levels was measured. Also, insulin resistance indexes were determined. OVA-sensitization and diet-induced obesity caused the curve of methacholine concentration response to shifting to the left. In addition, results indicated that the EC50 (the effective concentration of methacholine generating 50% of peak response) in F+SHFD rats was statistically lower than M+SHFD group (p<0.05). Moreover, insulin resistance was higher in the F+SHFD than the M+SHFD group (p<0.001). These results suggest that insulin resistance and metabolic syndrome may be involved in the pathogenesis of obesity associated with OVA-sensitized rats condition, especially in female animals.
Topics: Allergens; Animals; Asthma; Blood Glucose; Bronchoconstrictor Agents; Diet, High-Fat; Disease Models, Animal; Female; Insulin; Insulin Resistance; Male; Methacholine Chloride; Obesity; Ovalbumin; Rats, Wistar; Trachea
PubMed: 30848573
DOI: No ID Found -
American Journal of Physiology. Lung... Nov 2018Isolated human airway smooth muscle (ASM) tissue contractility studies are essential for understanding the role of ASM in respiratory disease, but limited availability...
Isolated human airway smooth muscle (ASM) tissue contractility studies are essential for understanding the role of ASM in respiratory disease, but limited availability and cost render storage options necessary for optimal use. However, to our knowledge, no comprehensive study of cryopreservation protocols for isolated ASM has been performed to date. We tested several cryostorage protocols on equine trachealis ASM using different cryostorage media [1.8 M dimethyl sulfoxide and fetal bovine serum (FBS) or Krebs-Henseleit (KH)] and different degrees of dissection (with or without epithelium and connective tissues attached) before storage. We measured methacholine (MCh), histamine, and isoproterenol (Iso) dose-responses and electrical field stimulation (EFS) and MCh force-velocity curves. We confirmed our findings in human trachealis ASM stored undissected in FBS. Maximal stress response to MCh was decreased more in dissected than undissected equine tissues. EFS force was decreased in all equine but not in human cryostored tissues. Furthermore, in human cryostored tissues, EFS maximal shortening velocity was decreased, and Iso response was potentiated after cryostorage. Overnight incubation with 0.5 or 10% FBS did not recover contractility in the equine tissues but potentiated Iso response. Overnight incubation with 10% FBS in human tissues showed maximal stress recovery and maintenance of other contractile parameters. ASM tissues can be cryostored while maintaining most contractile function. We propose an optimal protocol for cryostorage of ASM as undissected tissues in FBS or KH solution followed by dissection of the ASM bundles and a 24-h incubation with 10% FBS before mechanics measurements.
Topics: Animals; Cryopreservation; Cryoprotective Agents; Dimethyl Sulfoxide; Histamine; Horses; Methacholine Chloride; Muscle Contraction; Muscle, Smooth; Trachea
PubMed: 30091377
DOI: 10.1152/ajplung.00064.2018 -
The European Respiratory Journal Feb 2017Tidal breathing flow volume (TBFV) profiles have been used to characterise altered lung function. Impedance pneumography (IP) is a novel option for assessing TBFV curves...
Tidal breathing flow volume (TBFV) profiles have been used to characterise altered lung function. Impedance pneumography (IP) is a novel option for assessing TBFV curves noninvasively. The aim of this study was to extend the application of IP for infants and to estimate the agreement between IP and direct pneumotachograph (PNT) measurements in assessing tidal airflow and flow-derived indices.Tidal flow profiles were recorded for 1 min simultaneously with PNT and uncalibrated IP at baseline in 44 symptomatic infants, and after methacholine-induced bronchoconstriction in a subgroup (n=20).The agreement expressed as the mean deviation from linearity ranged between 3.9 and 4.3% of tidal peak inspiratory flow, but was associated with specific airway conductance (p=0.002) and maximal flow at functional residual capacity () (p=0.004) at baseline. Acute bronchoconstriction induced by methacholine did not significantly affect the agreement of IP with PNT. TBFV indices derived from IP were slightly underestimated compared to PNT, but were equally well repeatable and associated with baseline (p=0.012 and p=0.013, respectively).TBFV profiles were consistent between IP and PNT in most infants, but the agreement was affected by reduced lung function. TBFV parameters were not interchangeable between IP and PNT, but had a similar association with lung function in infants.
Topics: Airway Obstruction; Bronchoconstrictor Agents; Child, Preschool; Electric Impedance; Female; Functional Residual Capacity; Humans; Infant; Lung; Male; Methacholine Chloride; Respiratory Function Tests; Tertiary Care Centers; Tidal Volume
PubMed: 28182566
DOI: 10.1183/13993003.00926-2016 -
International Journal For Parasitology.... Aug 2023The nematode genome exhibits a vast array of Cys-loop receptors that are activated by a diverse set of neurotransmitters and anthelmintic drugs such as ivermectin and...
The nematode genome exhibits a vast array of Cys-loop receptors that are activated by a diverse set of neurotransmitters and anthelmintic drugs such as ivermectin and levamisole. While many Cys-loop receptors have been functionally and pharmacologically characterized, there remains a large subset of orphan receptors where the agonist remains unknown. We have identified an orphan Cys-loop receptor, LGC-39, from the parasitic nematode Haemonchus contortus that is a novel type of cholinergic-sensitive ligand-gated chloride channel. This receptor groups outside of the acetylcholine-gated chloride channel family, in the previously named GGR-1 (GABA/Glycine Receptor-1) group of Cys-loop receptors. We found that LGC-39 forms a functional homomeric receptor when expressed in Xenopus laevis oocytes and is activated by several cholinergic ligands including acetylcholine, methacholine and surprisingly, atropine with an EC for atropine on the low μM range. A homology model was generated which revealed some key features of the LGC-39 ligand-binding pocket that may explain some of the elements important for atropine recognition of the LGC-39 receptor. Overall these results suggest that the GGR-1 family (now called LGC-57) of Cys-loop receptors includes novel acetylcholine-gated chloride channel subtypes and may represent important future drug targets.
Topics: Animals; Chloride Channels; Acetylcholine; Haemonchus; Ligands; Receptors, GABA; Cysteine Loop Ligand-Gated Ion Channel Receptors; Ligand-Gated Ion Channels; Cholinergic Agents; Atropine Derivatives
PubMed: 37054482
DOI: 10.1016/j.ijpddr.2023.04.001 -
Respirology (Carlton, Vic.) Oct 2014Ventilation heterogeneity (VH) has been linked to airway responsiveness (AR) based on various measures of VH involving inert gas washout, forced oscillation and lung...
BACKGROUND AND OBJECTIVE
Ventilation heterogeneity (VH) has been linked to airway responsiveness (AR) based on various measures of VH involving inert gas washout, forced oscillation and lung imaging. We explore whether VH at baseline, as measured by the simple ratio of single breath alveolar volume to plethysmographically determined total lung capacity (VA/TLC), would correlate with AR as measured by methacholine challenge testing.
METHODS
We analysed data from spirometry, lung volumes, diffusing capacity and methacholine challenge to derive the VA/TLC and the dose-response slope (DRS) of forced expiratory volume in 1 s (DRS-FEV1) during methacholine challenge from 136 patients. We separated out airway closure versus narrowing by examining the DRS for forced vital capacity (DRS-FVC) and the DRS for FEV1/FVC (DRS-FEV1/FVC), respectively. Similarly, we calculated the DRS for sGaw (DRS-sGaw) as another measure of airway narrowing. We performed statistical analysis using Spearman rank correlation and multifactor linear regression using a backward stepwise modelling procedure.
RESULTS
We found that the DRS-FEV1 correlated with baseline VA/TLC (rho = -0.26, P < 0.01), and VA/TLC and FEV1 were independently associated with DRS-FEV1 (R(2) = 0.14, P = 0.01). In addition, VA/TLC was associated with both airway narrowing and closure in response to methacholine.
CONCLUSIONS
These results confirm that baseline VA/TLC is associated with AR, and reflects both airway closure and airway narrowing following methacholine challenge.
Topics: Adult; Aged; Airway Remodeling; Airway Resistance; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoconstrictor Agents; Cohort Studies; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Pulmonary Diffusing Capacity; Spirometry; Total Lung Capacity
PubMed: 24995907
DOI: 10.1111/resp.12347 -
Respirology (Carlton, Vic.) Jul 2019The reduction of forced expiratory volume in 1 s (FEV ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the...
BACKGROUND AND OBJECTIVE
The reduction of forced expiratory volume in 1 s (FEV ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV /forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC).
METHODS
We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV , and calculated as %ΔFVC/%ΔFEV .
RESULTS
There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control.
CONCLUSION
Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.
Topics: Administration, Inhalation; Adolescent; Adult; Age Factors; Asthma; Bronchial Provocation Tests; Bronchoconstrictor Agents; Child; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Middle Aged; Obesity; Vital Capacity; Young Adult
PubMed: 30838750
DOI: 10.1111/resp.13496 -
Journal of Aerosol Medicine and... Jun 2016Theoretical models suggest that He-O2 as carrier gas may lead to more homogeneous ventilation and aerosol deposition than air. However, these effects have not been...
BACKGROUND
Theoretical models suggest that He-O2 as carrier gas may lead to more homogeneous ventilation and aerosol deposition than air. However, these effects have not been clinically consistent and it is unclear why subjects may or may not respond to the therapy. Here we present 3D-imaging data of aerosol deposition and ventilation distributions from subjects with asthma inhaling He-O2 as carrier gas. The data are compared with those that we previously obtained from a similar group of subjects inhaling air.
METHODS
Subjects with mild-to-moderate asthma were bronchoconstricted with methacholine and imaged with PET-CT while inhaling aerosol carried with He-O2. Mean-normalized-values of lobar specific ventilation sV* and deposition sD* were derived and the factors affecting the distribution of sD* were evaluated along with the effects of breathing frequency (f) and regional expansion (FVOL).
RESULTS
Lobar distributions of sD* and sV* with He-O2 were not statistically different from those previously measured with air. However, with He-O2 there was a larger number of lobes having sV* and sD* closer to unity and, in those subjects with uneven deposition distributions, the correlation of sD* with sV* was on average higher (p < 0.05) in He-O2 (0.84 ± 0.8) compared with air (0.55 ± 0.28). In contrast with air, where the frequency of breathing during nebulization was associated with the degree of sD*-sV* correlation, with He-O2 there was no association. Also, the modulation of f on the correlation between FVOL and sD*/sV* in air, was not observed in He-O2.
CONCLUSION
There were no differences in the inter-lobar heterogeneity of sD* or sV* in this group of mild asthmatic subjects breathing He-O2 compared with patients previously breathing air. Future studies, using these personalized 3D data sets as input to CFD models, are needed to understand if, and for whom, breathing He-O2 during aerosol inhalation may be beneficial.
Topics: Administration, Inhalation; Adolescent; Aerosols; Asthma; Bronchoconstriction; Bronchoconstrictor Agents; Drug Carriers; Female; Gases; Helium; Humans; Imaging, Three-Dimensional; Inhalation; Isotonic Solutions; Lung; Male; Methacholine Chloride; Models, Biological; Nebulizers and Vaporizers; Oxygen; Positron Emission Tomography Computed Tomography; Pulmonary Ventilation; Sodium Chloride; Tissue Distribution; Young Adult
PubMed: 26824777
DOI: 10.1089/jamp.2014.1204 -
Experimental Physiology Aug 2023What is the central question of this study? The lung response to inhaled methacholine is reputed to be greater in male than in female mice. The underpinnings of this sex...
NEW FINDINGS
What is the central question of this study? The lung response to inhaled methacholine is reputed to be greater in male than in female mice. The underpinnings of this sex disparity are ill defined. What is the main finding and its importance? We demonstrated that male airways exhibit a greater content of airway smooth muscle than female airways. We also found that, although a more muscular airway tree in males might contribute to their greater responsiveness to inhaled methacholine than females, it might also curb the heterogeneity in small airway narrowing.
ABSTRACT
Mouse models are helpful in unveiling the mechanisms underlying sex disparities in asthma. In comparison to their female counterparts, male mice are hyperresponsive to inhaled methacholine, a cardinal feature of asthma that contributes to its symptoms. The physiological details and the structural underpinnings of this hyperresponsiveness in males are currently unknown. Herein, BALB/c mice were exposed intranasally to either saline or house dust mite once daily for 10 consecutive days to induce experimental asthma. Twenty-four hours after the last exposure, respiratory mechanics were measured at baseline and after a single dose of inhaled methacholine that was adjusted to trigger the same degree of bronchoconstriction in both sexes (it was twice as high in females). Bronchoalveolar lavages were then collected, and the lungs were processed for histology. House dust mite increased the number of inflammatory cells in bronchoalveolar lavages to the same extent in both sexes (asthma, P = 0.0005; sex, P = 0.96). The methacholine response was also markedly increased by asthma in both sexes (e.g., P = 0.0002 for asthma on the methacholine-induced bronchoconstriction). However, for a well-matched bronchoconstriction between sexes, the increase in hysteresivity, an indicator of airway narrowing heterogeneity, was attenuated in males for both control and asthmatic mice (sex, P = 0.002). The content of airway smooth muscle was not affected by asthma but was greater in males (asthma, P = 0.31; sex, P < 0.0001). These results provide further insights regarding an important sex disparity in mouse models of asthma. The increased amount of airway smooth muscle in males might contribute functionally to their greater methacholine response and, possibly, to their decreased propensity for airway narrowing heterogeneity.
Topics: Male; Female; Animals; Mice; Methacholine Chloride; Asthma; Lung; Bronchoconstriction; Muscle, Smooth
PubMed: 37341687
DOI: 10.1113/EP091236