The 2023 report of the MJA-Lancet Countdown on health and climate change: sustainability needed in Australia's health care sector.

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.

Acute Effects of Resistance Exercise on Intraocular Pressure in Healthy Adults: A Systematic Review.

ABSTRACT: Hackett, DA, Li, J, Wang, B, Way, KL, Cross, T, and Tran, DL. Acute effects of resistance exercise on intraocular pressure in healthy adults: A systematic review. J Strength Cond Res 38(2): 394-404, 2024-Intraocular pressure (IOP) tends to fluctuate during a resistance exercise (RE). This systematic review examines the acute effects of RE on IOP in healthy adults and factors that influence changes in IOP. Five electronic databases were searched using terms related to RE and IOP. A strict inclusion criterion was applied, which included being 55 years or younger with no medical conditions and RE intensity needing to be quantifiable (e.g., based on a maximal effort). Thirty-four studies met the inclusion criteria for this review. Isometric and isotonic contractions produced similar changes in IOP during RE up to 28.7 mm Hg. Exercises that involved larger muscle mass, such as squats and leg press, were found to produce changes in IOP during exercise ranging from 3.1 to 28.7 mm Hg. Smaller changes in IOP during RE were found for exercises engaging less muscle mass (e.g., handgrip and bicep curls). Intraocular pressure was found to increase during RE when lifting heavier loads and with longer exercise durations (e.g., greater repetitions). The Valsalva maneuver (VM) and breath-hold during RE accentuated the change in IOP, with more extreme changes observed with the VM. However, most studies showed that postexercise IOP returned to baseline after approximately 1 minute of recovery. An acute increase in IOP is observed during RE in healthy adults with fluctuations of varying magnitude. Factors that independently increase IOP during RE include exercises involving larger muscle mass, heavy loads, greater set duration, and when the VM or breath-hold is performed.

The effect of estimating chest wall compliance on the work of breathing during exercise as determined via the modified Campbell diagram.

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.

Exercise Intolerance in Heart Failure: Central Role for the Pulmonary System.

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.

Influence of ß2 adrenergic receptor genotype on risk of nocturnal ventilation in patients with Duchenne muscular dystrophy.

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.

Influence of Thoracic Fluid Compartments on Pulmonary Congestion in Chronic Heart Failure.

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.

Repeated-sprint cycling does not induce respiratory muscle fatigue in active adults: measurements from the powerbreathe® inspiratory muscle trainer.

This study examined respiratory muscle strength using the POWERbreathe® inspiratory muscle trainer (i.e., 'S-Index') before and after repeated-sprint cycling for comparison with maximal inspiratory pressure (MIP) values obtained during a Mueller maneuver. The S-Index was measured during six trials across two sessions using the POWERbreathe® and MIP was measured during three trials in a single session using a custom-made manometer in seven recreationally active adults. Global respiratory muscle strength was measured using both devices before and after the performance of sixteen, 6-s sprints on a cycle ergometer. Intraclass correlation coefficients for the POWERbreathe® S-index indicated excellent (p < 0.05) trial-to-trial (r = 0.87) and day-to-day (r = 0.90) reliability yet there was no significant correlation (r = -0.35, p = 0.43) between the S-Index measured using the POWERbreathe® and MIP measured during a Mueller maneuver. Repeated-sprint cycling had no effect on respiratory muscle strength as measured by the POWERbreathe® (p > 0.99) and during the Mueller maneuver (p > 0.99). The POWERbreathe® S-Index is a moderately reliable, but not equivalent, measure of MIP determined during a Mueller maneuver. Furthermore, repeated-sprint cycling does not induce globalized respiratory muscle fatigue in recreationally-active adults. Key pointsThe S-Index as measured by the POWERbreathe® is a reliable measure of respiratory muscle strengthThe S-Index does not accurately reflect maximal inspiratory pressure obtained from a Mueller maneuverRepeated-sprint cycling does not induce respiratory muscle fatigue as measured by the POWERbreathe® and the Manometer.

A single-session testing protocol to determine critical power and W'.

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.

Expiratory Threshold Loading and Attentional Performance.

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.

Differential effects of exercise intensity and tolerable duration on exercise-induced diaphragm and expiratory muscle fatigue.

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.

Exercise in bushfire smoke for high performance athletes: A Position Statement from the Australian Institute of SportEndorsed by Australasian College of Sport and Exercise Physicians (ACSEP) and Sport Medicine Australia (SMA).

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.

A Systematic Review of Methods Used to Determine the Work of Breathing during Exercise.

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.

The resistive and elastic work of breathing during exercise in patients with chronic heart failure.

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.

Evidence of break-points in breathing pattern at the gas-exchange thresholds during incremental cycling in young, healthy subjects.

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.

Inspiratory threshold loading negatively impacts attentional performance.

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.

Adverse events following influenza immunization: understanding the role of age and sex interactions.

BACKGROUND: Reduction of adverse events following immunization (AEFI) could improve vaccine uptake. Evidence suggests sex and age affect AEFI rates but, with limited understanding of their interaction, groups at higher risk for adverse reaction cannot be identified. RESEARCH DESIGN AND METHODS: Using deidentified data (n = 308,481) from Australians receiving influenza vaccinations in the 2020 calendar year, we analyzed the effects of independent predictors (i.e. age and sex), on experiencing an AEFI using logistic regression generalized additive modeling to capture any nonlinear relationships and adjusting for vaccine brand and concomitant vaccination. RESULTS: The overall reaction rate was 5.5%. Modeling revealed significant effects of age (p < 0.001), sex (p < 0.001), and age × sex (p < 0.001). Females were more likely than males to experience AEFIs between 7.5 and 87.5 years of age and exhibited peak odds at about 53 years, while peak odds for males occurred in infancy. CONCLUSION: The results suggest there is a need for targeting AEFI reduction in females, particularly in 30-70-year-olds, to improve the vaccination experience. The results further suggest that reducing concomitant vaccination and choosing less reactogenic vaccine brands could reduce risk of AEFI, however, retaining concomitant vaccination may optimize vaccine uptake.

Fixed Airflow Obstruction in Asthma: A Problem of the Whole Lung Not of Just the Airways.

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.

Influence of ß2 adrenergic receptor genotype on longitudinal measures of forced vital capacity in patients with Duchenne muscular dystrophy.

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.