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1.
Med J Aust ; 220(6): 282-303, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38522009

RESUMO

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017 and produced its first national assessment in 2018 and annual updates in 2019, 2020, 2021 and 2022. It examines five broad domains: health hazards, exposures and impacts; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In this, the sixth report of the MJA-Lancet Countdown, we track progress on an extensive suite of indicators across these five domains, accessing and presenting the latest data and further refining and developing our analyses. Our results highlight the health and economic costs of inaction on health and climate change. A series of major flood events across the four eastern states of Australia in 2022 was the main contributor to insured losses from climate-related catastrophes of $7.168 billion - the highest amount on record. The floods also directly caused 23 deaths and resulted in the displacement of tens of thousands of people. High red meat and processed meat consumption and insufficient consumption of fruit and vegetables accounted for about half of the 87 166 diet-related deaths in Australia in 2021. Correction of this imbalance would both save lives and reduce the heavy carbon footprint associated with meat production. We find signs of progress on health and climate change. Importantly, the Australian Government released Australia's first National Health and Climate Strategy, and the Government of Western Australia is preparing a Health Sector Adaptation Plan. We also find increasing action on, and engagement with, health and climate change at a community level, with the number of electric vehicle sales almost doubling in 2022 compared with 2021, and with a 65% increase in coverage of health and climate change in the media in 2022 compared with 2021. Overall, the urgency of substantial enhancements in Australia's mitigation and adaptation responses to the enormous health and climate change challenge cannot be overstated. Australia's energy system, and its health care sector, currently emit an unreasonable and unjust proportion of greenhouse gases into the atmosphere. As the Lancet Countdown enters its second and most critical phase in the leadup to 2030, the depth and breadth of our assessment of health and climate change will be augmented to increasingly examine Australia in its regional context, and to better measure and track key issues in Australia such as mental health and Aboriginal and Torres Strait Islander health and wellbeing.


Assuntos
Mudança Climática , Setor de Assistência à Saúde , Humanos , Austrália , Saúde Mental , Planejamento em Saúde
2.
Am J Physiol Regul Integr Comp Physiol ; 320(3): R268-R275, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356877

RESUMO

The modified Campbell diagram provides one of the most comprehensive assessments of the work of breathing (Wb) during exercise, wherein the resistive and elastic work of inspiration and expiration are quantified. Importantly, a necessary step in constructing the modified Campbell diagram is to obtain a value for chest wall compliance (CCW). To date, it remains unknown whether estimating or directly measuring CCW impacts the Wb, as determined by the modified Campbell diagram. Therefore, the purpose of this study was to evaluate whether the components of the Wb differ when the modified Campbell diagram is constructed using an estimated versus measured value of CCW. Forty-two participants (n = 26 men, 16 women) performed graded exercise to volitional exhaustion on a cycle ergometer. CCW was measured directly at rest via quasistatic relaxation. Estimated values of CCW were taken from prior literature. The measured value of CCW was greater than that obtained via estimation (214 ± 52 mL/cmH2O vs. 189 ± 18 mL/cmH2O; P < 0.05). At modest-to-high minute ventilations (i.e., 50-200 L/min), the inspiratory elastic Wb was greater and expiratory resistive Wb was lower, when modified Campbell diagrams were constructed using estimated compared with measured values of CCW (P = 0.001). These differences were however small and never exceeded ±5%. Thus, although our findings demonstrate that estimating CCW has a measurable impact on the determination of the Wb, its effect appears relatively small within a cohort of healthy adults during graded exercise.


Assuntos
Exercício Físico , Pulmão/fisiologia , Modelos Teóricos , Respiração , Músculos Respiratórios/fisiologia , Parede Torácica/fisiologia , Trabalho Respiratório , Adolescente , Adulto , Idoso , Ciclismo , Complacência (Medida de Distensibilidade) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
3.
Exerc Sport Sci Rev ; 48(1): 11-19, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31453845

RESUMO

We propose that abnormalities of the pulmonary system contribute significantly to the exertional dyspnea and exercise intolerance observed in patients with chronic heart failure. Interventions designed to address the deleterious pulmonary manifestations of heart failure may, therefore, yield promising improvements in exercise tolerance in this population.


Assuntos
Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/fisiologia , Pulmão/fisiopatologia , Pressão Sanguínea/fisiologia , Brônquios/irrigação sanguínea , Doença Crônica , Dispneia/fisiopatologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Pulmão/irrigação sanguínea , Músculo Esquelético/fisiopatologia , Consumo de Oxigênio/fisiologia , Prognóstico , Capacidade de Difusão Pulmonar , Troca Gasosa Pulmonar , Relação Ventilação-Perfusão , Trabalho Respiratório/fisiologia
5.
Respir Res ; 20(1): 221, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619245

RESUMO

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease resulting in severe respiratory derangements. As such, DMD patients are at a high risk of nocturnal hypoventilation, thereby requiring nocturnal ventilation (NV). To this end, NV is an important clinical milestone in the management of DMD. Emerging evidence suggests that ß2 adrenergic receptors (ADRB2) may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function and respiratory muscle strength. These findings suggest that the more functional ADRB2 genotype may help to preserve respiratory function in patients with DMD. The purpose of this study was to identify the influence of ADRB2 genotype on the risk of NV use in DMD. Data from the CINRG Duchenne Natural History Study including 175 DMD patients (3-25 yrs) were analyzed focusing on ADRB2 genotype variants. Time-to-event analyses were used to examine differences in the age at prescription of full-time NV use between genotypes. There were no differences between genotype groups in age, height, weight, corticosteroid use, proportion of ambulatory patients, or age at loss of ambulation. DMD patients expressing the Gly16 polymorphism had a significantly (P < 0.05) lower mean age at NV prescription compared with those patients expressing the Arg16 polymorphism (21.80 ± 0.59 yrs. vs 25.91 ± 1.31 yrs., respectively). In addition, a covariate-adjusted Cox model revealed that the Gly16 variant group possessed a 6.52-fold higher risk of full-time NV use at any given age compared with the Arg16 polymorphism group. These data suggest that genetic variations in the ADRB2 gene may influence the age at which DMD patients are first prescribed NV, whereby patients with the Gly16 polymorphism are more likely to require NV assistance at an earlier age than their Arg16 counterparts.


Assuntos
Genótipo , Hipoventilação/genética , Distrofia Muscular de Duchenne/genética , Polimorfismo Genético/genética , Receptores Adrenérgicos beta 2/genética , Respiração Artificial , Adolescente , Adulto , Criança , Pré-Escolar , Bases de Dados Genéticas , Humanos , Hipoventilação/diagnóstico , Hipoventilação/epidemiologia , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/epidemiologia , Respiração Artificial/tendências , Adulto Jovem
7.
J Card Fail ; 23(9): 690-696, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28716688

RESUMO

INTRODUCTION: Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh, respectively) and extravascular lung water (EVLW) change in stable HF and affect lung function. METHODS: Fourteen patients with HF (age 68 ± 11 y, LVEF 33 ± 8%) and 12 control subjects (age 65 ± 9 y) were recruited. A pulmonary function test, thoracic computerized tomographic (CT) scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max (FWHM) calculated as surrogates of EVLW. Blood volumes were calculated from the transit time of the contrast through the great vessels of the heart. RESULTS: Patients with HF had greater Vp and Vh (Vp 0.55 ± 0.21 L vs 0.41 ± 0.13 L; Vh 0.53 ± 0.33 L vs 0.40 ± 0.15 L) and EVLW (skew 3.2 ± 0.5 vs 3.7 ± 0.7; kurtosis 19.4 ± 6.6 vs 25.9 ± 9.4; FWHM 73 ± 13 HU vs 59 ± 9 HU). Spirometric measures were decreased in HF (percentage of predicted: forced vital capacity 86 ± 17% vs 104 ± 9%; forced expiratory volume in 1 second 83 ± 20% vs 105 ± 11%; maximal mid-expiratory flow 82 ± 42% vs 115 ± 43%). Vp was associated with decreased expiratory flows, and EVLW was associated with decreased lung volumes. CONCLUSIONS: Congestion in stable patients with HF includes expanded Vp and Vh and increased EVLW associated with reductions in lung volumes and expiratory flows.


Assuntos
Volume Sanguíneo/fisiologia , Água Extravascular Pulmonar/diagnóstico por imagem , Água Extravascular Pulmonar/fisiologia , Insuficiência Cardíaca/diagnóstico por imagem , Edema Pulmonar/diagnóstico por imagem , Volume de Ventilação Pulmonar/fisiologia , Idoso , Doença Crônica , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Edema Pulmonar/complicações , Edema Pulmonar/fisiopatologia , Tomografia Computadorizada por Raios X/tendências
8.
Eur J Appl Physiol ; 114(6): 1153-61, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24563054

RESUMO

PURPOSE: Critical power (CP), and the finite capacity to perform work above CP (W'), can be determined using a 3-min "all-out" cycling test (3MT). This protocol requires two laboratory visits: an incremental exercise test, followed by a 3MT on a separate day. The purpose of this study was to establish whether an incremental exercise test and a 3MT performed during a single laboratory visit can be used to accurately determine CP and W'. METHODS: Twelve participants completed two experimental protocols: (1) Combined protocol: an incremental exercise test followed by a 3MT, with 20 min of recovery between exercise bouts; and (2) Independent protocol: the conventional 3MT protocol, performed on a separate day. RESULTS: CP determined from the Combined (254 ± 117 W) and Independent (256 ± 118 W) protocols were not different (p = 0.40). Similarly, W' was not different (p = 0.96) between the Combined (13.7 ± 3.9 kJ) and Independent (13.7 ± 4.5 kJ) protocols. Linear regression revealed a strong level of measurement agreement between the protocols for CP and W', evidenced by high R(2) values (≥0.85) and marginal standard errors of the estimates (CP = 5 W; W' = 1.81 kJ). CONCLUSION: A Combined protocol, consisting of an incremental exercise test followed by a 3MT, provides an accurate and valid method to determine an individual's CP and, to a lesser extent, W'. Furthermore, this protocol permits the measurement of the gas-exchange threshold and peak O2 uptake and, consequently, the moderate, heavy, and severe exercise-intensity domains may be defined within a single exercise-testing session.


Assuntos
Teste de Esforço/métodos , Resistência Física , Adulto , Feminino , Humanos , Masculino , Aptidão Física
9.
Aerosp Med Hum Perform ; 95(7): 367-374, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38915161

RESUMO

INTRODUCTION: While there are numerous factors that may affect pilot attentional performance, we hypothesize that an increased expiratory work of breathing experienced by fighter pilots may impose a "distraction stimulus" by creating an increased expiratory effort sensation. Therefore, the purpose of this study was to determine the extent to which increasing expiratory pressure time product or expiratory effort sensation impacts attentional performance.METHODS: Data was collected on 10 healthy participants (age: 29 ± 6 yr). Participants completed six repetitions of a modified Masked Conjunctive Continuous Performance Task protocol while breathing against four different expiratory threshold loads. Repeated measures analysis of variances and generalized additive mixed effects models were used to investigate the effects of expiratory threshold load conditions on expiratory pressure time product, expiratory effort sensation, and the influence of altered end tidal gases on Masked Conjunctive Continuous Performance Task scores.RESULTS: The overall median hit reaction times were significantly longer as the expiratory threshold loads increased. Specific shape-conjunctive and non-conjunctive median hit reaction times were longer with increased expiratory effort sensation. Additionally, increased expiratory effort sensation did not significantly change commission error rates, but did significantly increase omission error rates.DISCUSSION: The findings of our work suggest that both progressively greater expiratory threshold loads during spontaneous breathing and expiratory effort sensation may impair subjects' attentional performance due to longer reaction times and increased stimuli recognition error rates.Kelley EF, Cross TJ, Johnson BD. Expiratory threshold loading and attentional performance. Aerosp Med Hum Perform. 2024; 95(7):367-374.


Assuntos
Atenção , Humanos , Adulto , Atenção/fisiologia , Masculino , Adulto Jovem , Expiração/fisiologia , Tempo de Reação/fisiologia , Feminino , Análise e Desempenho de Tarefas , Pilotos/psicologia
10.
J Appl Physiol (1985) ; 136(6): 1591-1603, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38695354

RESUMO

We investigated the effect of exercise intensity and tolerable duration on the development of exercise-induced diaphragm and expiratory muscle fatigue. Ten healthy adults (25 ± 5 yr; 2 females) cycled to intolerance on three separate occasions: 1) 5% below critical power ( 0.05). In conclusion, the magnitude of exercise-induced diaphragm fatigue was greater after longer-duration severe exercise than after shorter-duration severe and heavy exercise. By contrast, the magnitude of exercise-induced expiratory muscle fatigue was unaffected by exercise intensity and tolerable duration.NEW & NOTEWORTHY Exercise-induced respiratory muscle fatigue contributes to limiting exercise tolerance. Accordingly, better understanding the exercise conditions under which respiratory muscle fatigue occurs is warranted. Although heavy-intensity as well as short- and long-duration severe-intensity exercise performed to intolerance elicit diaphragm and expiratory muscle fatigue, we find, for the first time, that the relationship between exercise intensity, exercise duration, and the magnitude of exercise-induced fatigue is different for the diaphragm compared with the expiratory muscles.


Assuntos
Diafragma , Exercício Físico , Fadiga Muscular , Humanos , Fadiga Muscular/fisiologia , Masculino , Feminino , Diafragma/fisiologia , Diafragma/fisiopatologia , Adulto , Exercício Físico/fisiologia , Adulto Jovem , Consumo de Oxigênio/fisiologia , Músculos Respiratórios/fisiologia , Expiração/fisiologia
11.
J Sci Med Sport ; 26(2): 98-108, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36858652

RESUMO

OBJECTIVES: The frequency of bushfires in Australia is increasing and it is expected bushfire smoke will become a more prevalent phenomenon impacting air quality. The objective of this position statement is to provide guidance to the sport sector regarding exercise in air affected by bushfire smoke. DESIGN: This is position statement from the Australian Institute of Sport, based on a narrative review of the literature regarding bushfire smoke and its effects on health and exercise performance. METHODS: A narrative review of scientific publications regarding the effects of bushfire smoke on health and exercise performance. RESULTS: Bushfire smoke has negative impacts on health and performance. Athletes exercising at high intensity over a prolonged duration will increase their exposure to air pollutants. Athletes with a history of elevated airway responsiveness are likely to be at increased risk of an adverse response to bushfire smoke exposure. CONCLUSIONS: Athletes, coaches, support staff and sport organisations should monitor air quality (PM2.5 concentration) and make appropriate adjustments to training duration and intensity.


Assuntos
Médicos , Medicina Esportiva , Humanos , Fumaça , Austrália , Atletas
12.
Med Sci Sports Exerc ; 55(9): 1672-1682, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37126027

RESUMO

INTRODUCTION: Measurement of the work of breathing (Wb) during exercise provides useful insights into the energetics and mechanics of the respiratory muscles across a wide range of minute ventilations. The methods and analytical procedures used to calculate the Wb during exercise have yet to be critically appraised in the literature. PURPOSE: The aim of this systematic review was to evaluate the quality of methods used to measure the Wb during exercise in the available literature. METHODS: We conducted an extensive search of three databases for studies that measured the Wb during exercise in adult humans. Data were extracted on participant characteristics, flow/volume and pressure devices, esophageal pressure (P oes ) catheters, and methods of Wb analysis. RESULTS: A total of 120 articles were included. Flow/volume sensors used were primarily pneumotachographs ( n = 85, 70.8%), whereas the most common pressure transducer was of the variable reluctance type ( n = 63, 52.5%). Esophageal pressure was frequently obtained via balloon-tipped catheters ( n = 114, 95.0%). Few studies mentioned calibration, frequency responses, and dynamic compensation of their measurement devices. The most popular method of measuring the Wb was pressure-volume integration ( n = 51, 42.5%), followed by the modified Campbell ( n = 28, 23.3%) and Dean & Visscher diagrams ( n = 26, 21.7%). Over one-third of studies did not report the methods used to process their pressure-volume data, and the majority (60.8%) of studies used the incorrect Wb units and/or failed to discuss the limitations of their Wb measurements. CONCLUSIONS: The findings of this systematic review highlight the need for the development of a standardized approach for measuring Wb, which is informative, practical, and accessible for future researchers.


Assuntos
Respiração , Trabalho Respiratório , Adulto , Humanos , Trabalho Respiratório/fisiologia , Exercício Físico/fisiologia , Músculos Respiratórios/fisiologia
13.
Eur Respir J ; 39(6): 1449-57, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22034652

RESUMO

Patients with heart failure (HF) display numerous derangements in ventilatory function, which together serve to increase the work of breathing (W(b)) during exercise. However, the extent to which the resistive and elastic properties of the respiratory system contribute to the higher W(b) in these patients is unknown. We quantified the resistive and elastic W(b) in patients with stable HF (n = 9; New York Heart Association functional class I-II) and healthy control subjects (n = 9) at standardised levels of minute ventilation (V'(E)) during graded exercise. Dynamic lung compliance was systematically lower for a given level of V'(E) in HF patients than controls (p<0.05). HF patients displayed slightly higher levels of inspiratory elastic W(b) with greater amounts of ventilatory constraint and resistive W(b) than control subjects during exercise (p<0.05). Our data indicates that the higher W(b) in HF patients is primarily due to a greater resistive, rather than elastic, load to breathing. The greater resistive W(b) in these patients probably reflects an increased hysteresivity of the airways and lung tissues. The marginally higher inspiratory elastic W(b) observed in HF patients appears related to a combined decrease in the compliances of the lungs and chest wall. The clinical and physiological implications of our findings are discussed.


Assuntos
Exercício Físico/fisiologia , Insuficiência Cardíaca/fisiopatologia , Trabalho Respiratório/fisiologia , Doença Crônica , Elasticidade , Teste de Esforço , Feminino , Humanos , Pulmão/fisiopatologia , Complacência Pulmonar/fisiologia , Masculino , Pessoa de Meia-Idade
14.
Eur J Appl Physiol ; 112(3): 1067-76, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21735217

RESUMO

The present study investigated whether 'break-points' in breathing pattern correspond to the first ([Formula: see text]) and second gas-exchange thresholds ([Formula: see text]) during incremental cycling. We used polynomial spline smoothing to detect accelerations and decelerations in pulmonary gas-exchange data, which provided an objective means of 'break-point' detection without assumption of the number and shape of said 'break-points'. Twenty-eight recreational cyclists completed the study, with five individuals excluded from analyses due to low signal-to-noise ratios and/or high risk of 'pseudo-threshold' detection. In the remaining participants (n = 23), two separate and distinct accelerations in respiratory frequency (f (R)) during incremental work were observed, both of which demonstrated trivial biases and reasonably small ±95% limits of agreement (LOA) for the [Formula: see text] (0.2 ± 3.0 ml O(2) kg(-1) min(-1)) and [Formula: see text] (0.0 ± 2.4 ml O(2) kg(-1) min(-1)), respectively. A plateau in tidal volume (V (T)) data near the [Formula: see text] was identified in only 14 individuals, and yielded the most unsatisfactory mean bias ±LOA of all comparisons made (-0.4 ± 5.3 ml O(2) kg(-1) min(-1)). Conversely, 18 individuals displayed V (T)-plateau in close proximity to the [Formula: see text] evidenced by a mean bias ± LOA of 0.1 ± 3.1 ml O(2) kg(-1) min(-1). Our findings suggest that both accelerations in f (R) correspond to the gas-exchange thresholds, and a plateau (or decline) in V (T) at the [Formula: see text] is a common (but not universal) feature of the breathing pattern response to incremental cycling.


Assuntos
Ciclismo/fisiologia , Oxigênio/metabolismo , Troca Gasosa Pulmonar/fisiologia , Respiração , Adulto , Fatores Etários , Limiar Anaeróbio/fisiologia , Teste de Esforço/métodos , Feminino , Saúde , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Adulto Jovem
15.
Front Psychol ; 13: 959515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186373

RESUMO

Rationale: There are growing concerns over the occurrence of adverse physiologic events (PEs) occurring in pilots during operation of United States Air Force and Navy high-performance aircraft. We hypothesize that a heightened inspiratory work of breathing experienced by jet pilots by virtue of the on-board life support system may constitute a "distraction stimulus" consequent to an increased sensation of respiratory muscle effort. As such, the purpose of this study was to determine whether increasing inspiratory muscle effort adversely impacts on attentional performance. Methods: Twelve, healthy participants (age: 29 ± 6 years) were recruited for this study. Participants completed six repetitions of a modified Masked Conjunctive Continuous Performance Task (MCCPT) protocol while breathing against four different inspiratory threshold loads to assess median reaction times (RTs). A computer-controlled threshold loading device was used to set the inspiratory threshold loads. Repeated measures analysis of variances (ANOVAs) were performed to examine: (i) the efficacy of the threshold loading device to impose significantly higher loading at each loading condition; (ii) the effects of loading condition on respiratory muscle effort sensation; and (iii) the influence of hypercapnia on MCCPT scores during inspiratory threshold loading. Generalized additive mixed effects models (GAMMs) were used to examine the potential non-linear effects of respiratory muscular effort sensation, device loading, and hypercapnia, on MCCPT scores during inspiratory threshold loading. Results: Inspiratory threshold loading significantly augmented (P < 0.05) inspiratory effort sensation and the inspiratory pressure-time product (PTP). Our analyses also revealed that median hit RT was positively associated with inspiratory effort sensation during inspiratory loading trials. Conclusion: The findings of this work suggest that it was not increasing inspiratory muscle effort (i.e., PTP) per se, but rather participant's subjective perception of inspiratory "load" that impacts negatively on attentional performance; i.e., as the degree of inspiratory effort sensation increased, sotoo did median hit RT. As such, it is reasonable to suggest that minimizing inspiratory effort sensation (independent of the mechanical output of the inspiratory muscles) during high-performance flight operations may prove useful in reducing pilot RTs during complex behavioral tasks.

16.
Front Physiol ; 13: 898208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677089

RESUMO

Asthma with irreversible or fixed airflow obstruction (FAO) is a severe clinical phenotype that is difficult to treat and is associated with an accelerated decline in lung function and excess morbidity. There are no current treatments to reverse or prevent this excessive decline in lung function in these patients, due to a lack of understanding of the underlying pathophysiology. The current paradigm is that FAO in asthma is due to airway remodeling driven by chronic inflammation. However, emerging evidence indicates significant and critical structural and functional changes to the lung parenchyma and its lung elastic properties in asthma with FAO, suggesting that FAO is a 'whole lung' problem and not just of the airways. In this Perspective we draw upon what is known thus far on the pathophysiological mechanisms contributing to FAO in asthma, and focus on recent advances and future directions. We propose the view that structural and functional changes in parenchymal tissue, are just as (if not more) important than airway remodeling in causing persistent lung function decline in asthma. We believe this paradigm of FAO should be considered when developing novel treatments.

17.
Neuromuscul Disord ; 32(2): 150-158, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35115229

RESUMO

The progression of decline in forced vital capacity as percent predicated (FVC%p) is a strong indicator of worsening prognosis in patients with Duchenne muscular dystrophy (DMD). Evidence suggests that ß2 adrenergic (ADRB2) receptors may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function. The purpose of this study was to determine the influence of ADRB2 genotype on longitudinal measures of FVC%p as a function of age in DMD patients. Data from the CINRG Duchenne Natural History Study including 169 DMD patients (5-25 yrs) were analyzed. A generalized additive mixed effects model was used to examine differences in the nonlinear trend of FVC%p across patient ages between genotype groups after controlling for patient demographics, corticosteroid-use, and ambulatory status. Both genotype groups displayed a progressive, maturational decline in FVC%p. Notwithstanding this decline, patients expressing the Gly16 polymorphism demonstrated systematically lower FVC%p values at any given age compared with patients expressing the Arg16 polymorphism (P < 0.01). Therefore, expressing the Gly16 polymorphism may prove detrimental to respiratory function in DMD patients. These data suggest maybe ADRB2 genotyping should be considered in the clinical management of DMD patients.


Assuntos
Distrofia Muscular de Duchenne , Genótipo , Humanos , Respiração , Transdução de Sinais , Capacidade Vital
18.
Clin Med Insights Cardiol ; 16: 11795468221116838, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046180

RESUMO

The purpose of this study was to determine whether the longitudinal progression of decline in left ventricular ejection fraction (LVEF) in Duchenne muscular dystrophy (DMD) patients is moderated by ADRB1 genotype and whether the efficacy of ß-blocker therapy is influenced by genotype status. About 147 DMD patients (6-34 years.) were analyzed with a focus on ß1 adrenergic receptor (ADRB1) genotype variants. Patients were grouped by ADRB1 genotype resulting in Gly389 patients and Arg389 patients. A generalized additive mixed effects model was used to examine differences in the nonlinear trend of LVEF across patient ages between genotype groups and for ß-blocker use. Both genotype groups displayed a progressive decline in LVEF starting around the mean age of ambulation loss (~12 years). However, there was no difference between genotype groups in the progression of decline in LVEF. There was a significant effect of ß-blocker use on longitudinal LVEF, wherein patients on ß-blockers had systematically lower LVEF when compared to patients not on ß-blockers. However, the effect of ß-blocker therapy on LVEF was not affected by ADRB1 genotype. The current study did not demonstrate an influence of patient ADRB1 genotype on longitudinal LVEF in our cohort. Despite previous literature suggesting a positive influence of ß-blocker use on cardiac function in DMD patients and of an ADRB1 genotypic difference in responsiveness to ß-blocker use, we did not observe this in our cohort. Interestingly, our cohort did not demonstrate a positive influence of ß-blocker use on LVEF measures.

20.
Sci Rep ; 11(1): 918, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441688

RESUMO

We describe here a novel protocol that sequentially combines venous followed by arterial occlusions to determine muscle blood flow and O2 uptake from a single measurement point using near-infrared spectroscopy (NIRS) during handgrip exercise. NIRS data were obtained from the flexor digitorum superficialis (FDS) muscle on the dominant arm of 15 young, healthy adults (3 women; 26 ± 7 years; 78.6 ± 9.1 kg). Participants completed a series of 15-s static handgrip contractions at 20, 40 and 60% of maximal voluntary contraction (MVC) immediately followed by either a: (i) venous occlusion (VO); (ii); arterial occlusion (AO); or venous then arterial occlusion (COMBO). Each condition was repeated 3 times for each exercise-intensity. The concordance correlation coefficient (CCC) and robust linear mixed effects modeling were used to determine measurement agreement between vascular occlusion conditions. FDS muscle blood flow ([Formula: see text]) and conductance ([Formula: see text]) demonstrated strong absolute agreement between VO and COMBO trials from rest up to 60%MVC, as evidenced by high values for CCC (> 0.82) and a linear relationship between conditions that closely approximated the line-of-identity (perfect agreement). Conversely, although FDS muscle O2 uptake ([Formula: see text]) displayed "substantial" to "near perfect" agreement between methods across exercise intensities (i.e., CCC > 0.80), there was a tendency for COMBO trials to underestimate [Formula: see text] by up to 7%. These findings indicate that the COMBO method provides valid estimates of [Formula: see text] and, to a slightly lesser extent, [Formula: see text] at rest and during static handgrip exercise up to 60%MVC. Practical implications and suggested improvements of the method are discussed.


Assuntos
Circulação Sanguínea/fisiologia , Músculo Esquelético/irrigação sanguínea , Consumo de Oxigênio/fisiologia , Adulto , Exercício Físico/fisiologia , Feminino , Antebraço , Mãos/fisiologia , Força da Mão/fisiologia , Hemodinâmica , Humanos , Masculino , Músculo Esquelético/metabolismo , Músculos/irrigação sanguínea , Músculos/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Veias/fisiologia , Adulto Jovem
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