The asthma-obesity relationship: underlying mechanisms and treatment implications.

PURPOSE OF REVIEW: Obesity is a worldwide epidemic with a prevalence that has tripled in the last two decades. Worldwide, more than 1.5 billion adults are overweight and more than 500 million obese. Obesity has been suggested to be a risk factor for the development of more difficult-to-control asthma. Although the mechanisms underlying the asthma-obesity relationship are not fully understood, several possible explanations have been put forward. These will be reviewed in this manuscript as well as the implications for the treatment of overweight and obese asthma patients. RECENT FINDINGS: Insulin resistance is a possible factor contributing to the asthma-obesity relationship and the effect is independent of other components of the metabolic syndrome such as hypertriglyceridemia, hypertension, hyperglycemia, and systemic inflammation. Obesity has important effects on airway geometry, by especially reducing expiratory reserve volume causing obese asthmatics to breathe at low lung volumes. Furthermore, obesity affects the type of inflammation in asthma and is associated with reduced inhaled corticosteroids treatment responsiveness. SUMMARY: Obesity induces the development of asthma with a difficult-to-control phenotype. Treatment targeting insulin resistance may be beneficial in obese asthma patients, especially when they have concomitant diabetes. Systemic corticosteroids should be avoided as much as possible as they are not very effective in obese asthma and associated with side-effects like diabetes, weight gain, and osteoporosis.

Cardiovascular and respiratory effects of the neoprene wetsuit in non-immersed divers.

A neoprene wetsuit is widely used to reduce thermal dispersion during diving. Recent observations have pointed out that elastic recoil of the wetsuit might have significant compressive effects, able to affect water and electrolyte homeostasis during both dry and immersed conditions. The aim of this study was to evaluate the possible cardiovascular and respiratory effects of the neoprene wetsuit in dry conditions in a sample of experienced divers. Twenty-four (24) healthy divers were evaluated by Doppler-echocardiography and by spirometry in basal conditions and while wearing a full neoprene wetsuit. During wetsuit conditions, we observed a significant decrease in heart rate (-5%; p ⟨ 0.05) and cardiac output (-12%; p ⟨ 0.05), and a significant increase in total peripheral resistances (15%; p ⟨ 0.05). Moreover, a significant reduction of right ventricular early diastolic filling was observed (-15%; p ⟨ 0.05). As concerns pulmonary function, a significant reduction of vital capacity (-2%; p ⟨ 0.001) and expiratory reserve volume (-25%; p ⟨ 0.001), and a significant increase of inspiratory capacity (9%; p ⟨ 0.001) and tidal volume (25%; p ⟨ 0.05) were observed. These data support the hypothesis that neoprene elastic recoil, possibly due to a compression exerted on chest, might affect systemic circulation (decreasing cardiac output and impairing right ventricular filling) and respiratory function.

What can impulse oscillometry and pulmonary function testing tell us about obstructive sleep apnea: a case-control observational study?

PURPOSE: This study aims to determine whether functional residual capacity (FRC) in obese patients with obstructive sleep apnea (OSA) decreases more than in patients without OSA because of decreased outward recoil from chest wall mass loading as well as increased lung inward recoil. METHODS: Subjects who were overweight and obese to various degrees with normal spirometric values underwent overnight polysomnography to determine the presence or absence of OSA and were labeled as cases or controls. Lung volume and respiratory mechanical properties were measured by plethysmograph and impulse oscillometry, respectively. RESULTS: A total of 76 men and 31 women were diagnosed with OSA (cases); 64 men and 33 women without OSA were confirmed as controls. Expiratory reserve volume and FRC were significantly decreased in cases compared with controls. Respiratory impedance and resistance at 5 Hz were significantly higher in cases than in controls, although reactance at low frequencies was significantly lower in cases than in controls. Reactance at 5 Hz (Xrs5) was found to be independently highly correlated with the severity of OSA as defined by the Apnea-Hypopnea Index and was significantly correlated with FRC. CONCLUSIONS: FRC is significantly decreased in overweight or obese patients with OSA compared with those without OSA, which may be attributed to an increase in lung elastic recoil. The stronger correlation between Xrs5 and OSA severity might indicate upper airway stenosis, and abnormally increased lung elastic recoil may contribute to OSA.

OPTIMUM LEVEL OF POSITIVE END-EXPIRATORY PRESSURE IN ACUTE RESPIRATORY DISTRESS SYNDROME CAUSED BY INFLUENZA A(H1NI)PDM09: BALANCE BETWEEN MAXIMAL END-EXPIRATORY VOLUME AND MINIMAL ALVEOLAR OVERDISTENSION.

THE AIM: to determine optimum level ofpositive end-expiratory pressure (PEEP) according to balance between maxi- mal end-expiratory lung volume (EEL V)(more than predicted) and minimal decrease in exhaled carbon dioxide volume (VCO) and then to develop the algorithm of gas exchange correction based on prognostic values of EEL K; alveolar recruitability, PA/FiO2, static compliance (C,,,) and VCO2. MATERIALS AND METHODS: 27 mechanically ventilatedpatients with acute respiratory distress syndrome (ARDS) caused by influenza A (HINJ)pdm09 in Moscow Municipal Clinics ICU's from January to March 2016 were included in the trial. At the beginning of the study patients had the following characteristic: duration offlu symptoms 5 (3-10) days, p.0/FiO2 120 (70-50) mmHg. SOFA 7 (5-9), body mass index 30.1 (26.4-33.8) kg/m², static compliance of respiratory system 35 (30-40) ml/mbar: Under sedation and paralysis we measured EELV, C VCO and end-tidal carbon dioxide concentration (EtCO) (for CO2 measurements we fixed short-term values after 2 min after PEEP level change) at PEEP 8, 11,13,15,18, 20 mbar consequently, and incase of good recruitability, at 22 and 24 mbar. After analyses of obtained data we determined PEEP value in which increase in EELV was maximal (more than predicted) and depression of VCO2 was less than 20%, change in mean blood pressure and heart rate were both less than 20% (measured at PEEP 8 mbar). After that we set thus determined level of PEEP and didn't change it for 5 days. RESULTS: Comparision of predicted and measured EELV revealed two typical points of alveloar recruiment: the first at PEEP 11-15 mbar, the second at PEEP 20-22 mbar. EELV measured at PEEP 18 mbar appeared to be higher than predicted at PEEP 8 mbar by 400 ml (approx.), which was the sign of alveolar recruitment-1536 (1020-1845) ml vs 1955 (1360-2320) ml, p=0,001, Friedman test). we didn't found significant changes of VCO2 when increased PEEP in the range from 8 to 15 mbar (p>0.05, Friedman test). PEEP increase from 15 to 18 mbar and more lead to decrease in VCO2 (from 212 (171-256) ml/min to 200 (153-227) ml/min, p<0,0001, Friedman test, which was the sign of overdistension. Next decrease of VCO2 was observed at PEEP increase from 22 to 24 mbar (from 203 (174-251 ml/min) to 185 (182-257) ml/min, p=0.0025, Friedman test). Adjusted PEEP value according to balance between recruitment and overdistension was higher than the one initially set (16(15-18) mbar vs 12(7-15) mbar, p <0.0001). We observed increase of SpO2 from 93 (87-96) to 97(95-100)% (p<0.0001 followed by decrease in inspiratory oxygen fraction from 60(40-80) to 50(40-60)%(p<0.0001). Low EELV VCO2 and VCO2/EtCO2 at PEEP 8 mbar has low predictive value for death (AUROC 0,547, 0706 and 0.596, respectively).Absolute EELV value at PEEP 18 and 20 mbar were poor predictors of mortality (AUROC 0.61 and 0.65 respectively) Alveolar recruit ability was measured by subtraction of EELV at PEEP 20 and at PEEP II mbar - value below 575 ml was a good predictor of death (sensitivity 75%, specificity 88%, AUROC 0.81). Lowering of VCO2 at PEEP 20 mbar to less than 207 ml/min was a marker of alveolar overdistension and associated with poor prognosis (sensitivity 83%, specificity 88%, AUROC 0,89). C has poor predictive value at PEEP 8 and 20 mbar (AUROC 0,58 and 0,74 respectively. Conclusion: PEEP adjustment in ARDS due to influenza A (H1N1) pdm09 in accordance with balance between recruitment and overdistension (based on EELV and VCO measurements) can improve gas exchange, probably, not leading to right ventricular failure. This value of "balanced" PEEP is in the range between 15 and 18 mbar: Low lung recruitabiilty is associated with poor prognosis. Measurements of EELV and VCO2 at PEEP 8 and 20 mbar can be used to make a decision on whether to keep "high" PEEP level or switch to extracorporeal membrane oxygenation in patient with ARDS due to influenza A (N1H1).

Endurance exercise performance in acute hypoxia is influenced by expiratory flow limitation.

PURPOSE: We sought to determine if expiratory flow limitation influences intensive aerobic exercise performance in mild hypoxia. METHODS: Fourteen trained male cyclists were separated into flow-limited (FL, n = 7) and non-FL (n = 7) groups based on the extent of expiratory flow limitation exhibited during maximal exercise in normoxia. Participants performed two self-paced 5-km cycling time trials, one in normoxic (F IO2 = 0.21) and one in mild hypoxic (F IO2 = 0.17) conditions in a randomized, balanced order with the subjects blinded to composition of the inspirate. Percent change from normoxia to hypoxia in average power output (%ΔP TT) and time to completion (%ΔT TT) were used to assess performance. RESULTS: Hypoxia resulted in a significant decline in estimated arterial O2 saturation and decrements in performance in both groups, although FL had a significantly smaller %ΔP TT (-4.0 ± 0.5 vs. -9.0 ± 1.8 %) and %ΔT TT (1.3 ± 0.3 vs. 3.7 ± 0.9 %) compared to non-FL. At the 5th km of the time trial, minute ventilation did not change from normoxia to hypoxia in FL (3.4 ± 3.1 %) or non-FL (2.3 ± 3.7 %), but only the non-FL reported a significantly increased dyspnea rating in hypoxia compared to normoxia (~9 %). Non-FL athletes did not utilize their ventilatory reserve to defend arterial oxygen saturation in hypoxia, which may have been due to an increased measure of dyspnea in the hypoxic trial. CONCLUSION: FL athletes experience less hypoxia-related aerobic exercise performance impairment as compared to non-FL athletes, despite having less ventilatory reserve.

Lung recruitment and endotracheal suction in ventilated preterm infants measured with electrical impedance tomography.

AIMS: Although suctioning is a standard airway maintenance procedure, there are significant associated risks, such as loss of lung volume due to high negative suction pressures. This study aims to assess the extent and duration of change in end-expiratory level (EEL) resulting from endotracheal tube (ETT) suction and to examine the relationship between EEL and regional lung ventilation in ventilated preterm infants with respiratory distress syndrome. METHODS: A prospective observational clinical study of the effect of ETT suction on 20 non-muscle-relaxed preterm infants with respiratory distress syndrome (RDS) on conventional mechanical ventilation was conducted in a neonatal intensive care unit. Ventilation distribution was measured with regional impedance amplitudes and EEL using electrical impedance tomography. RESULTS: ETT suction resulted in a significant increase in EEL post-suction (P < 0.01). Regionally, anterior EEL decreased and posterior EEL increased post-suction, suggesting heterogeneity. Tidal volume was significantly lower in volume-guarantee ventilation compared with pressure-controlled ventilation (P = 0.04). CONCLUSIONS: ETT suction in non-muscle-relaxed and ventilated preterm infants with RDS results in significant lung volume increase that is maintained for at least 90 min. Regional differences in distribution of ventilation with ETT suction suggest that the behaviour of the lung is heterogeneous in nature.

Generalized anxiety disorder is associated with reduced lung function in the Vietnam Experience Study.

BACKGROUND: There is no clear consensus in the few studies to have explored the relationship between major mental health disorders and lung function. The present study examined the cross-sectional associations of generalized anxiety disorder (GAD) and major depressive disorder (MDD) with lung function in a large study of male US veterans. METHODS: Participants (N = 4256) were drawn from the Vietnam Experience Study. From military files, telephone interviews, and a medical examination, anthropometric, sociodemographic, and health data were collected. One-year prevalence of GAD and MDD was determined using DSM-III criteria. Forced expiratory volume in 1 second was measured by spirometry. RESULTS: In models that adjusted for age and height, both GAD (p < .001) and MDD (p = .004) were associated with lower forced expiratory volume in 1 second. In models additionally adjusting for weight, place of service, ethnicity, marriage, smoking, alcohol consumption, income, education, and major illness, GAD was still associated with poorer lung function (p = .01), whereas MDD was not (p = .18). CONCLUSIONS: Depression has very much been the focus of studies on mental health and physical health status. The current findings suggest that future research should perhaps pay equal attention to GAD.

End-expiratory lung volume and ventilation distribution with different continuous positive airway pressure systems in volunteers.

BACKGROUND: Continuous positive airway pressure (CPAP) has been shown to improve oxygenation and a number of different CPAP systems are available. The aim of this study was to assess lung volume and ventilation distribution using three different CPAP techniques. METHODS: A high-flow CPAP system (HF-CPAP), an ejector-driven system (E-CPAP) and CPAP using a Servo 300 ventilator (V-CPAP) were randomly applied at 0, 5 and 10 cmH2O in 14 volunteers. End-expiratory lung volume (EELV) was measured by N2 dilution at baseline; changes in EELV and tidal volume distribution were assessed by electric impedance tomography. RESULTS: Higher end-expiratory and mean airway pressures were found using the E-CPAP vs. the HF-CPAP and the V-CPAP system (P<0.01). EELV increased markedly from baseline, 0 cmH2O, with increased CPAP levels: 1110±380, 1620±520 and 1130±350 ml for HF-, E- and V-CPAP, respectively, at 10 cmH2O. A larger fraction of the increase in EELV occurred for all systems in ventral compared with dorsal regions (P<0.01). In contrast, tidal ventilation was increasingly directed toward dorsal regions with increasing CPAP levels (P<0.01). The increase in EELV as well as the tidal volume redistribution were more pronounced with the E-CPAP system as compared with both the HF-CPAP and the V-CPAP systems (P<0.05) at 10 cmH2O. CONCLUSION: EELV increased more in ventral regions with increasing CPAP levels, independent of systems, leading to a redistribution of tidal ventilation toward dorsal regions. Different CPAP systems resulted in different airway pressure profiles, which may result in different lung volume expansion and tidal volume distribution.

Intraoperative recruitment maneuver reverses detrimental pneumoperitoneum-induced respiratory effects in healthy weight and obese patients undergoing laparoscopy.

BACKGROUND: Pulmonary function is impaired during pneumoperitoneum mainly as a result of atelectasis formation. We studied the effects of 10 cm H2O of positive end-expiratory pressure (PEEP) and PEEP followed by a recruitment maneuver (PEEP+RM) on end-expiratory lung volume (EELV), oxygenation and respiratory mechanics in patients undergoing laparoscopic surgery. METHODS: Sixty consecutive adult patients (30 obese, 30 healthy weight) in reverse Trendelenburg position were prospectively studied. EELV, static elastance of the respiratory system, dead space, and gas exchange were measured before and after pneumoperitoneum insufflation with zero end-expiratory pressure, with PEEP alone, and with PEEP+RM. Results are presented as mean ± SD. RESULTS: Pneumoperitoneum reduced EELV (healthy weight, 1195 ± 405 vs. 1724 ± 774 ml; obese, 751 ± 258 vs. 886 ± 284 ml) and worsened static elastance and dead space in both groups (in all P < 0.01 vs. zero-end expiratory pressure before pneumoperitoneum) whereas oxygenation was unaffected. PEEP increased EELV (healthy weight, 570 ml, P < 0.01; obese, 364 ml, P < 0.01) with no effect on oxygenation. Compared with PEEP alone, EELV and static elastance were further improved after RM in both groups (P < 0.05), as was oxygenation (P < 0.01). In all patients, RM-induced change in EELV was 16% (P = 0.04). These improvements were maintained 30 min after RM. RM-induced changes in EELV correlated with change in oxygenation (r = 0.42, P < 0.01). CONCLUSION: RM combined with 10 cm H2O of PEEP improved EELV, respiratory mechanics, and oxygenation during pneumoperitoneum whereas PEEP alone did not.

Increasing ventilator surge capacity in COVID 19 pandemic: design, manufacture and in vitro-in vivo testing in anaesthetized healthy pigs of a rapid prototyped mechanical ventilator.

OBJECTIVE: The advent of new technologies has made it possible to explore alternative ventilator manufacturing to meet the worldwide shortfall for mechanical ventilators especially in pandemics. We describe a method using rapid prototyping technologies to create an electro-mechanical ventilator in a cost effective, timely manner and provide results of testing using an in vitro-in vivo testing model. RESULTS: Rapid prototyping technologies (3D printing and 2D cutting) were used to create a modular ventilator. The artificial manual breathing unit (AMBU) bag connected to wall oxygen source using a flow meter was used as air reservoir. Controlled variables include respiratory rate, tidal volume and inspiratory: expiratory (I:E) ratio. In vitro testing and In vivo testing in the pig model demonstrated comparable mechanical efficiency of the test ventilator to that of standard ventilator but showed the material limits of 3D printed gears. Improved gear design resulted in better ventilator durability whilst reducing manufacturing time (< 2-h). The entire cost of manufacture of ventilator was estimated at 300 Australian dollars. A cost-effective novel rapid prototyped ventilator for use in patients with respiratory failure was developed in < 2-h and was effective in anesthetized, healthy pig model.

Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea.

STUDY OBJECTIVES: Many patients with obstructive sleep apnea (OSA) have spontaneous periods of stable flow limited breathing during sleep without respiratory events or arousals. In addition, OSA is often more severe during REM than NREM and more severe during stage 2 than slow wave sleep (SWS). The physiological mechanisms for these observations are unknown. Thus we aimed to determine whether the activity of two upper airway dilator muscles (genioglossus and tensor palatini) or end-expiratory lung volume (EELV) differ between (1) spontaneously occurring stable and cyclical breathing and (2) different sleep stages in OSA. DESIGN: Physiologic observation. SETTING: Sleep physiology laboratory. STUDY PARTICIPANTS: 15 OSA patients with documented periods of spontaneous stable breathing. INTERVENTION: Subjects were instrumented with intramuscular electrodes for genioglossus and tensor palatini electromyograms (EMG(GG) and EMG(TP)), chest and abdominal magnetometers (EELV measurement), an epiglottic pressure catheter (respiratory effort), and a mask and pneumotachograph (airflow/ventilation). Patients slept supine overnight without CPAP. MEASUREMENTS AND RESULTS: Peak and Tonic EMG(GG) were significantly lower during cyclical (85.4 +/- 2.7 and 94.6 +/- 4.7 % total activity) than stable breathing (109.4 +/- 0.4 and 103 +/- 0.8% total activity, respectively). During respiratory events in REM, tonic EMG(GG) activity was lower than during respiratory events in stage 2 (71.9 +/- 5.1 and 119.6 +/- 5.6% total activity). EMG(GG) did not differ between stable stage 2 and stable SWS (98.9 +/- 3.2 versus 109.7 +/- 4.4% total activity), nor did EMG(TP) or EELV differ in any breathing condition/sleep stage. CONCLUSIONS: Increased genioglossus muscle tone is associated with spontaneous periods of stable flow limited breathing in the OSA subjects studied. Reductions in genioglossus activity during REM may explain the higher severity of OSA in that stage. Increased lung volume and tensor palatini activity do not appear to be major mechanisms enabling spontaneous stable flow limited breathing periods.

Comparison of energy expenditure, economy, and pedometer counts between normal weight and overweight or obese women during a walking and jogging activity.

This study compared energy expenditure (EE), economy of movement, and pedometer counts between normal weight and overweight or obese women during a treadmill walking and jogging activity. Participants were 13 normal weight (BMI 22.2 +/- 2.0 kg m(-2)) and 13 overweight or obese (BMI 27.2 +/- 2.1 kg m(-2)) women and all were non-smokers, not regularly active, and able to run 1.609 km continuously at 2.23 m s(-1). Each participant reported to the laboratory on three separate days within a 1-week period. During the first visit, tests for resting metabolic rate via indirect calorimetry, anthropometric measures, and VO(2)max were completed. On the subsequent two visits, participants were randomized to perform either a 1.609-km walk at 1.34 m s(-1) or a 1.609-km jog at 2.23 m s(-1). During each physical activity trial, all participants wore a pedometer to assess steps taken. EE during the 1.609-km walk was 280 +/- 29 kJ for the normal weight and 356 +/- 42 kJ for the overweight/obese women and during the 1.609-km jog was 393 +/- 46 kJ for the normal weight and 490 +/- 59 kJ for the overweight/obese women. In both trials, EE was statistically greater in the overweight/obese women. Economy of movement was not statistically different between the normal weight and overweight/obese women during the walk or jog. In both groups, pedometer counts were lower during the jog than the walk (P < 0.05). These data indicate significant differences in EE between normal weight and overweight/obese women during both a walking and jogging activity.

Effect of expiratory positive airway pressure on sleep disordered breathing.

STUDY OBJECTIVES: We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients. DESIGN: Observational physiology study PARTICIPANTS: We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H2O EPAP in random order, while measuring EELV and breathing pattern. RESULTS: The mean EELV change between baseline and EPAP was only 13.3 mL (range 2-25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64 +/- 0.54 vs 2.16 +/- 0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44 +/- 1.47 sec vs 3.73 +/- 0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9 +/- 4.17 L/min vs 9.05 +/- 2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6 +/- 28.7 and 56.8 +/- 30.3 events per hour (P = 0.4). CONCLUSION: In OSA patients during sleep, the application of 10 cm H2O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.

Fat distribution and end-expiratory lung volume in lean and obese men and women.

BACKGROUND: Although obesity significantly reduces end-expiratory lung volume (EELV), the relationship between EELV and detailed measures of fat distribution has not been studied in obese men and women. To investigate, EELV and chest wall fat distribution (ie, rib cage, anterior subcutaneous abdominal fat, posterior subcutaneous fat, and visceral fat) were measured in lean men and women (ie, < 25% body fat) and obese men and women (ie, > 30% body fat). METHODS: All subjects underwent pulmonary function testing, hydrostatic weighing, and MRI scans. Data were analyzed for the men and women separately by independent t test, and the relationships between variables were determined by regression analysis. RESULTS: All body composition measurements were significantly different among the lean and obese men and women (p < 0.001). However, with only a few exceptions, fat distribution was similar among the lean and obese men and women (p > 0.05). The mean EELV was significantly lower in the obese men (39 +/- 6% vs 46 +/- 4% total lung capacity [TLC], respectively; p < 0.0005) and women (40 +/- 4% vs 53 +/- 4% TLC, respectively; p < 0.0001) compared with lean control subjects. Many estimates of body fat were significantly correlated with EELV for both men and women. CONCLUSIONS: In both men and women, the decrease in EELV with obesity appears to be related to the cumulative effect of increased chest wall fat rather than to any specific regional chest wall fat distribution. Also, with only a few exceptions, relative fat distribution is markedly similar between lean and obese subjects.

The effects of obesity on lung volumes and oxygenation.

INTRODUCTION: Obesity can cause hypoxemia by decreasing lung volumes to where there is closure of lung units during normal breathing. Studies describing this phenomenon are difficult to translate into clinical practice. We wanted to determine the lung volume measurements that are associated with hypoxemia in obese patients, and explore how we could use these measurements to identify them. METHODS: We collected pulmonary function test results and arterial blood gas data on 118 patients without obstruction on pulmonary function testing. We included only patients with normal chest imaging and cardiac testing within one year of the pulmonary function test, to exclude other causes of hypoxemia. RESULTS: We found that as BMI increases, the mean paO2, ERV % predicted, and ERV/TLC decrease (BMI 20-30 kg/m2: paO2=90±8 mmHg, ERV% predicted 112±50, ERV/TLC (%) 19.7±6.5; BMI 30-40 kg/m2: paO2=84±10 mmHg, ERV% predicted 84±40 ERV/TLC(%) 13.6±7.6; BMI>40 kg/m2: paO2 78 ±12 mmHg, ERV% predicted 64±27 ERV/TLC(%) 11.4±5.8, ANOVA p<0.001). The A-a gradient increases as BMI increases (r=0.42, p<0.001). This correlation was stronger in men (r=0.54) than in women (r=0.35). The paO2 is lower in patients with a low ERV than in those with a normal ERV (p<0.001). In a multivariate linear regression, only the ERV/TLC predicted (%), age, and BMI were associated with oxygenation (r2 for A-a gradient =0.28, p=0.036). CONCLUSIONS: In obese patients without cardiopulmonary disease, oxygen levels decrease as BMI increases. This effect is associated with the obesity-related reduction in ERV and is independent of hypoventilation.

The effects of body mass index on lung volumes.

BACKGROUND: Obesity is a major health issue in North America, and the trend is for obesity to be a more important medical issue in the future. Since obesity can cause respiratory symptoms, many obese people are referred for pulmonary function tests (PFTs). It is well known that obesity causes decreases in lung volumes, but there has never been a large study showing the correlation between body mass index (BMI) and the various lung volumes. DESIGN: We collected PFT results from 373 patients sent for lung function testing who had normal values for airway function but a wide range of BMIs. SETTING: The PFTs were done in two accredited outpatient laboratories. RESULTS: There were significant linear relationships between BMI and vital capacity and total lung capacity, but the group mean values remained within the normal ranges even for morbidly obese patients. However, functional residual capacity (FRC) and expiratory reserve volume (ERV) decreased exponentially with increasing BMI, such that morbid obesity resulted in patients breathing near their residual volume. An important finding was that the greatest rates of change in FRC and ERV occurred in the overweight condition and in mild obesity. At a BMI of 30 kg/m2, FRC and ERV were only 75% and 47%, respectively, of the values for a lean person with a BMI of 20 kg/m2. CONCLUSIONS: We showed that BMI has significant effects on all of the lung volumes, and the greatest effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. Our results will assist clinicians when interpreting PFT results in patients with normal airway function.

Simulated obesity-related changes in lung volume increases airway responsiveness in lean, nonasthmatic subjects.

STUDY OBJECTIVE: To determine if obesity-related changes in lung volume might contribute to airway reactivity, we investigated the effects of simulated mild obesity-related lung volume reductions on airway responsiveness in lean, nonasthmatic subjects. PARTICIPANTS AND METHODS: We simulated the lung volume reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally mass loading the chest wall and abdomen, and shifting blood volume into the lung with lower limb compression (LLC). Airway responsiveness was assessed by measuring FEV(1) before and after methacholine challenge tests (1, 2.5, 5, 10, and 25 mg/mL) with the following: (1) no intervention (control); (2) external chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung function was measured before and after CL, LLC, and COMB were applied. RESULTS: The application of CL, LLC, and COMB decreased expiratory reserve volume, functional residual capacity, and total lung capacity compared with baseline. FVC and FEV(1) decreased significantly with CL and COMB, while FEV(1)/FVC did not change compared to baseline. The maximal response to the methacholine challenge increased with CL, LLC, and COMB, with a mean maximal fall of FEV(1) of 9%, 11%, and 18%, respectively, compared to a 6% fall with control. CONCLUSIONS: We conclude that decreases in lung volume increase airway responsiveness and may account for the increased propensity for increased airway responsiveness in the obese.

Increased propensity for apnea in response to acute elevations in left atrial pressure during sleep in the dog.

Periodic breathing is commonly observed in chronic heart failure (CHF) when pulmonary capillary wedge pressure is abnormally high and there is usually concomitant tachypneic hyperventilation. We hypothesized that acute pulmonary hypertension at pressures encountered in CHF and involving all of the lungs and pulmonary vessels would predispose to apnea/unstable breathing during sleep. We tested this in a chronically instrumented, unanesthetized dog model during non-rapid eye movement (NREM) sleep. Pulmonary hypertension was created by partial occlusion of the left atrium by means of an implanted balloon catheter in the atrial lumen. Raising mean left atrial pressure by 5.7 +/- 1.1 Torr resulted immediately in tachypneic hyperventilation [breathing frequency increased significantly from 13.8 to 19.9 breaths/min; end-tidal P(CO2) (P(ET(CO2))) fell significantly from 38.5 to 35.9 Torr]. This tachypneic hyperventilation was present during wakefulness, NREM sleep, and rapid eye movement sleep. In NREM sleep, this increase in left atrial pressure increased the gain of the ventilatory response to CO2 below eupnea (1.3 to 2.2 l.min(-1).Torr(-1)) and thereby narrowed the CO2 reserve [P(ET(CO2)) (apneic threshold) - P(ET(CO2)) (eupnea)], despite the decreased plant gain resulting from the hyperventilation. We conclude that acute pulmonary hypertension during sleep results in a narrowed CO2 reserve and thus predisposes toward apnea/unstable breathing and may, therefore, contribute to the breathing instability observed in CHF.

Overweight Is an Independent Risk Factor for Reduced Lung Volumes in Myotonic Dystrophy Type 1.

BACKGROUND: In this large observational study population of 105 myotonic dystrophy type 1 (DM1) patients, we investigate whether bodyweight is a contributor of total lung capacity (TLC) independent of the impaired inspiratory muscle strength. METHODS: Body composition was assessed using the combination of body mass index (BMI) and fat-free mass index. Pulmonary function tests and respiratory muscle strength measurements were performed on the same day. Patients were stratified into normal (BMI < 25 kg/m(2)) and overweight (BMI ≥ 25 kg/m(2)) groups. Multiple linear regression was used to find significant contributors for TLC. RESULTS: Overweight was present in 59% of patients, and body composition was abnormal in almost all patients. In overweight patients, TLC was significantly (p = 2.40×10(-3)) decreased, compared with normal-weight patients, while inspiratory muscle strength was similar in both groups. The decrease in TLC in overweight patients was mainly due to a decrease in expiratory reserve volume (ERV) further illustrated by a highly significant (p = 1.33×10(-10)) correlation between BMI and ERV. Multiple linear regression showed that TLC can be predicted using only BMI and the forced inspiratory volume in 1 second, as these were the only significant contributors. CONCLUSIONS: This study shows that, in DM1 patients, overweight further reduces lung volumes, as does impaired inspiratory muscle strength. Additionally, body composition is abnormal in almost all DM1 patients.

Interaction between the canine diaphragm and intercostal muscles in lung expansion.

Changes in intrathoracic pressure produced by the various inspiratory intercostals are essentially additive, but the interaction between these muscles and the diaphragm remains uncertain. In the present study, this interaction was assessed by measuring the changes in airway opening (DeltaPao) or transpulmonary pressure (DeltaPtp) in vagotomized, phrenicotomized dogs during spontaneous inspiration (isolated intercostal contraction), during isolated rectangular or ramp stimulation of the peripheral ends of the transected C(5) phrenic nerve roots (isolated diaphragm contraction), and during spontaneous inspiration with superimposed phrenic nerve stimulation (combined diaphragm-intercostal contraction). With the endotracheal tube occluded at functional residual capacity, DeltaPao during combined diaphragm-intercostal contraction was nearly equal to the sum of the DeltaPao produced by the two muscle groups contracting individually. However, when the endotracheal tube was kept open, DeltaPtp during combined contraction was 123% of the sum of the individual DeltaPtp (P < 0.001). The increase in lung volume during combined contraction was also 109% of the sum of the individual volume increases (P < 0.02). Abdominal pressure during combined contraction was invariably lower than during isolated diaphragm contraction. It is concluded, therefore, that the canine diaphragm and intercostal muscles act synergistically during lung expansion and that this synergism is primarily due to the fact that the intercostal muscles reduce shortening of the diaphragm. When the lung is maintained at functional residual capacity, however, the synergism is obscured because the greater stiffness of the rib cage during diaphragm contraction enhances the DeltaPao produced by the isolated diaphragm and reduces the DeltaPao produced by the intercostal muscles.