A Longitudinal Study of Respiratory Mechanics in Pregnant Women with Obesity and Overweight.

PURPOSE: Respiratory mechanics and the role of sex hormones in pregnancy are not well elucidated. We examined longitudinal and positional changes in lung mechanics in pregnancy and investigated the role of sex hormones. METHODS: A longitudinal study enrolled 135 women with obesity in early pregnancy. Fifty-nine percent of women identified as White; median body mass index at enrollment was 34.4 kg/m2. Women with respiratory disease were excluded. We obtained measurements of airway resistance and respiratory system reactance in various positions using impedance oscillometry and sex hormones in early and late pregnancy. RESULTS: With pregnancy progression, there was a significant increase in resonant frequency (Fres) (p = 0.012), integrated area of low frequency reactance (AX) (p = 0.0012) and R5-R20Hz (p = 0.038) in the seated position, and a significant increase in R5Hz (p = 0.000), Fres (p = 0.001), AX (p < 0.001 = 0.000), and R5-R20Hz (p = 0.014) in the supine position. Compared to the seated position, the supine position was associated with a significant increase in R5Hz, R20Hz, X5Hz, Fres, and AX in early (p-values < 0.026) and late pregnancy (p-values ≤ 0.001). Changes in progesterone levels between early and late pregnancy predicted the change in R5, Fres, and AX (p-values ≤ 0.043). CONCLUSION: Resistive and elastic loads increase with pregnancy progression and a change in body position from seated to supine increases resistive and elastic loads in both early and late pregnancies. The increase in airway resistance is primarily related to an increase in peripheral rather than central airways resistance. There was an association between the change in progesterone levels and airway resistance.

Pulmonary function testing in neuromuscular disease.

Neuromuscular disorders frequently compromize pulmonary function and effective ventilation, and a thorough respiratory evaluation often can assist in diagnosis, risk assessment, and prognostication. Since many of these disorders can be progressive, serial assessments may be necessary to best define a trajectory of impairment or improvement with therapy. Patients with neuromuscular diseases may have few respiratory symptoms and limited signs of skeletal muscle weakness, but can have significant respiratory muscle weakness. A single testing modality may fail to elucidate true respiratory compromise, and often a combination of tests is recommended to fully evaluate these patients. Common tests performed in this population include measurement of flow rates, lung volumes, maximal pressures, and airways resistance. This review covers the major respiratory testing modalities available in the evaluation of these patients, emphasizing both the benefits and shortcomings of each approach. The majority of parameters are available in a standard pulmonary laboratory (flows, volumes, static pressures), although referral to a specialized center may be necessary to conclusively evaluate a given patient.

The Utility of Diaphragm Ultrasound in Reducing Time to Extubation.

PURPOSE: Prediction of optimal timing for extubation of mechanically ventilated patients is challenging. Ultrasound measures of diaphragm thickness or diaphragm dome excursion have been used to aid in predicting extubation success or failure. The aim of this study was to determine if incorporating results of diaphragm ultrasound into usual ICU care would shorten the time to extubation. METHODS: We performed a prospective, randomized, controlled study at three Brown University teaching hospitals. Included subjects underwent block randomization to either usual care (Control) or usual care enhanced with ultrasound measurements of the diaphragm (Intervention). The primary outcome was the time to extubation after ultrasound, and the secondary outcome was the total days on the ventilator. Only intensivists in the Intervention group would have the ultrasound information on the likelihood of successful extubation available to incorporate with traditional clinical and physiologic measures to determine the timing of extubation. RESULTS: A total of 32 subjects were studied; 15 were randomized into the Control group and 17 into the Intervention group. The time from ultrasound to extubation was significantly reduced in the Intervention group compared to the Control group in patients with a ∆tdi% ≥ 30% (4.8 ± 8.4 vs 35.0 ± 41.0 h, p = 0.04). The time from ultrasound to extubation was shorter in subjects with a normally functioning diaphragm (∆tdi% ≥ 30%) compared to those with diaphragm dysfunction (∆tdi% < 30%) (23.2 ± 35.2 vs 57.3 ± 52.0 h p = 0.046). When combining the Intervention and Control groups, a value of ∆tdi% ≥ 30% for extubation success at 24 h provided a sensitivity, specificity, PPV and NPV of 90.9%, 86.7%, 90.9%, and 86.7%, respectively. CONCLUSIONS: Diaphragm ultrasound evaluation of ∆tdi% aids in reducing time to extubation.

End-expiratory lung volume decreases during REM sleep despite continuous positive airway pressure.

PURPOSE: Patients with obstructive sleep apnea (OSA) may experience apneas and hypopneas primarily during stage R (REM) sleep when end-expiratory lung volume (EELV) reaches its nadir. The purpose of this study was to determine if REM-related reductions in EELV persist in the presence of continuous positive airway pressure (CPAP) prescribed during non-stage REM (NREM) sleep. METHODS: We prospectively recruited 17 subjects referred to the sleep laboratory for CPAP titration. CPAP was titrated per AASM protocol to control respiratory events. The change in EELV was measured using magnetometry. RESULTS: Of the 17 subjects, 12 (71%) had moderate to severe OSA. Despite the application of CPAP, there was a significant reduction in EELV between NREM and REM sleep (- 105.9 ± 92.2 to - 325.0 ± 113.1 mL, respectively, p < 0.01). The change in EELV between non-stage R (NREM) and REM significantly correlated with overall apnea-hypopnea index (AHI) (r = 0.5, p = 0.04), the number of respiratory arousals during REM (r = 0.5, p = 0.04), and prescribed level of CPAP (r = 0.7, p < 0.01). CONCLUSION: REM-related reductions in EELV are associated with worsening sleep disordered breathing and occur despite the presence of CPAP.

Assessing Diaphragm Function in Chest Wall and Neuromuscular Diseases.

Diaphragm dysfunction is defined as the partial or complete loss of diaphragm muscle contractility. However, because the diaphragm is one of only a few skeletal muscles that is not amenable to direct examination, the tools available for the clinician to assess diaphragm function have been limited. Traditionally, measures of lung volume, inspiratory muscle strength, and radiographic techniques such as fluoroscopy have provided the major method to assess diaphragm function. Measurement of transdiaphragmatic pressure provides the most direct means of evaluating the diaphragm, but this technique is not readily available to clinicians. Diaprhragm ultrasonography is new method that allows for direct examination of the diaphragm.

Disorders of the Diaphragm.

Pathologic processes that involve the central nervous system, phrenic nerve, neuromuscular junction, and skeletal muscle can impair diaphragm function. When these processes are of sufficient severity to cause diaphragm dysfunction, respiratory failure may be a consequence. This article reviews basic diaphragm anatomy and physiology and then discusses diagnostic and therapeutic approaches to disorders that result in unilateral or bilateral diaphragm dysfunction. This discussion provides a context in which disorders of the diaphragm and their implications on respiratory function can be better appreciated.

Prospective Association of Physical Activity and Heart Failure Hospitalizations Among Black Adults With Normal Ejection Fraction: The Jackson Heart Study.

BACKGROUND: Given high rates of obesity, hypertension, and diabetes mellitus, black persons are at risk to develop heart failure. The association of moderate to vigorous physical activity (MVPA) and heart failure in black adults is underresearched. The purpose of this study was to explore whether greater MVPA was associated with lower risk of heart failure hospitalizations (HFHs) among black adults with normal ejection fractions. METHODS AND RESULTS: We performed a prospective analysis of 4066 black adults who participated in the Jackson Heart Study and who had physical activity measured, had normal ejection fraction on 2-dimensional echocardiograms, and were followed for 7 years for incident HFH. We used Cox proportional regression analyses adjusted for age, sex, body mass index, smoking status, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, coronary heart disease, atrial fibrillation, and chronic kidney disease and examined effect modification by sex and body mass index. Of the eligible population, 1925 participants, according to the duration of MVPA, had poor health (0 minutes/week), 1332 had intermediate health (1-149 minutes/week), and 809 had ideal health (≥150 minutes/week). There were 168 incident HFHs. MVPA for intermediate and ideal health was associated with decreasing risk of incident HFH (hazard ratio: 0.70 [95% confidence interval, 49-1.00] and 0.35 [95% confidence interval, 0.19-0.64], respectively; Ptrend=0.003). The full model revealed hazard ratios of 0.74 [95% confidence interval, 0.52-1.07] and 0.41 [95% confidence interval, 0.22-0.74], respectively. There was no effect modification between MVPA and body mass index or sex on incident HFH. CONCLUSIONS: A dose-response relationship between increasing levels of MVPA and protection from incident HFH was found in black men and women with normal ejection fractions.

Change in End-Expiratory Lung Volume During Sleep in Patients at Risk for Obstructive Sleep Apnea.

STUDY OBJECTIVES: As lung volume decreases radial traction on the upper airway is reduced, making it more collapsible. The purpose of this study was to measure change in end-expiratory lung volume (EELV) following sleep onset and to evaluate the relationship between change in EELV and sleep-disordered breathing. METHODS: Twenty subjects underwent overnight polysomnography, of whom 14 (70%) had obstructive sleep apnea (OSA). Change in EELV was measured throughout the night using magnetometry. Sleep was staged and respiratory events scored using American Academy of Sleep Medicine criteria. An additional 10 subjects had change in EELV measured simultaneously by magnetometer and spirometer while awake. RESULTS: In the subjects studied while awake, change in EELV calculated from magnetometer data correlated very strongly (r = 0.89, P < .001) with that obtained by spirometry. In the 20 subjects who underwent polysomnography, there was a decline in EELV for sleep stages N1, N2, N3, and R (REM sleep); 17.9 ± 121.0 mL (mean ± standard deviation), 228.5 ± 151.8 mL, 198.1 ± 122.1 mL, and 316.7 ± 131.9 mL, respectively. Mean EELV reduction during stage R sleep doubled that noted during non-stage R sleep (316.7 ± 131.9 mL versus 150.9 ± 89.7 mL, respectively) (P < .001). The difference in EELV between non-stage R and stage R sleep inversely correlated with mean oxygen saturation (r = -0.56, P = .06). EELV reduction in individuals with moderate and severe OSA was greater than in those with mild SDB but did not reach statistical significance. CONCLUSIONS: Magnetometry provides a precise, unobtrusive, and continuous means to study lung volume changes during sleep. EELV declines from sleep onset, reaching its nadir during stage R sleep. The reduction in EELV in stage R sleep was associated with lower mean oxygen saturation but was not associated with greater sleep-disordered breathing.

The Maximal Expiratory-to-Inspiratory Pressure Ratio and Supine Vital Capacity as Screening Tests for Diaphragm Dysfunction.

PURPOSE: The change in vital capacity from the seated to supine position (∆VC-supine) is used to screen for diaphragm dysfunction (DD), but some individuals are unable to tolerate the supine position. Since expiratory muscle function is often preserved in patients with isolated DD and inspiratory strength is reduced, the purpose of this study was to examine if the ratio of maximal expiratory pressure to maximal inspiratory pressure (MEP/MIP) may provide an alternative to ∆VC-supine when screening patients for DD. METHODS: We performed a cross-sectional analysis on 76 patients referred for evaluation of unexplained dyspnea and possible DD. MEP and MIP were measured in the seated position as well as the percent change in VC from the seated to supine position (∆VC-supine %). The presence of unilateral diaphragm paralysis (UDP), bilateral diaphragm paralysis (BDP), or normal diaphragm function (N) was confirmed by ultrasound. RESULTS: Of the 76 patients, 23 had N, 40 had UDP, and 13 had BDP. MEP/MIP was significantly greater for UDP compared to N (2.1(1.2-5.7) and 1.5(0.7-2.2), respectively) (median and interquartile range) and for BDP compared to UDP (4.3(2.3-7.5) and 2.1(1.2-5.7), respectively) (p < 0.001). The area (AUC) under the receiver-operating characteristic curve for MEP/MIP between N and UDP was 0.84 (95% confidence interval (CI) 0.74-0.94) and between UDP and BDP was 0.90 (95% CI 0.80-0.99). MEP/MIP had a strong monotonic relationship with ∆VC-supine % (Spearman's ρ = 0.68, p < 0.001). CONCLUSIONS: The MEP/MIP ratio provides a method with comparable sensitivity and specificity to ∆VC-supine % that can be used to screen patients with suspected isolated phrenic neuropathy and alleviates the need for measuring supine pulmonary function.

Change in Diaphragmatic Thickness During the Respiratory Cycle Predicts Extubation Success at Various Levels of Pressure Support Ventilation.

PURPOSE: Ultrasonographic assessment of diaphragm function with patients on low levels of pressure support (PS) predicts extubation outcomes, but similar information regarding extubation success under other conditions is lacking. The purpose of this study was to determine whether ultrasound (US) measurements of the diaphragm made on various levels of PS can predict time until successful extubation. METHODS: Fifty-six intubated patients underwent ultrasound of the right hemidiaphragm during a PS wean at varying levels of pressure support (PS 5/5 cm of H2O, 10/5 cm of H2O, and 15/5 cm of H2O). The diaphragm was visualized using a 7.5-10 mHz transducer in the zone of apposition of the diaphragm to the lower rib cage. The percent change in diaphragm thickness between end-expiration and end-inspiration (∆tdi%) was calculated at each level of PS. RESULTS: ∆tdi% >20 is a robust predictor of extubation success within 48 h of US at PS 5/5 cm of H2O and 10/5 cm of H2O (sensitivity 84.6 and 88.9 % and specificity 79.0 and 75.0 %, respectively). At PS greater than 10/5 cm of H2O, its predictive power was greatly diminished. Of nine patients who were extubated with ∆tdi% below the cutoff, 66.6 % required emergent reintubation in the next two days. CONCLUSIONS: Diaphragm US is a valid predictor of extubation success at some but not all PS settings. Using a ∆tdi% of 20 % on PS levels up to 10/5 cm of H2O may reduce both unnecessarily prolonged intubations and prevent emergent reintubations.

Association of obstructive sleep apnea risk factors with nocturnal enuresis in postmenopausal women.

OBJECTIVE: The prevalence of obstructive sleep apnea (OSA) in women increases significantly after menopause. However, identifying at-risk women is difficult because they tend to underreport symptoms and their complaints may differ from those traditionally associated with OSA. We investigated whether OSA risk factors are associated with the presence of a "nontraditional" complaint, such as nocturnal enuresis, in postmenopausal women. METHODS: A cross-sectional study of postmenopausal women aged 50 to 79 years who participated in the Women's Health Initiative Observational Study and clinical trials (1993-2005) at 40 clinical centers in the United States was performed. Multiple variable logistic regression analysis was used to determine the association of OSA risk factors with nocturnal enuresis. RESULTS: A cohort of 2,789 women (1.7%) reported having nocturnal enuresis. Obesity (odds ratio [OR], 2.29; 95% CI, 2.00-2.62), snoring (OR, 2.01; 95% CI, 1.74-2.32), poor sleep quality (OR, 1.70; 95% CI, 1.52-1.91), sleep fragmentation (OR, 2.44; 95% CI, 2.14-2.79), daytime sleepiness (OR, 1.50; 95% CI, 1.33-1.68), and hypertension (OR, 1.13; 95% CI, 1.01-1.26) were associated with nocturnal enuresis. Each additional OSA risk factor in a predefined OSA score significantly increased the odds of having nocturnal enuresis in a dose-response fashion (OR of 1.38, 2.00, 2.80, 3.87, 5.10, and 7.02 for scores of 1-6, respectively) compared with no risk factors. CONCLUSIONS: OSA risk factors are associated with nocturnal enuresis in postmenopausal women. Mechanisms relating nocturnal enuresis to OSA may include apnea-associated changes in intrathoracic pressure, leading to increased urine output. Questioning at-risk postmenopausal women presenting with nocturnal enuresis about other OSA risk factors should be considered.

End-Expiratory Volume and Oxygenation: Targeting PEEP in ARDS Patients.

INTRODUCTION: Changes in end-expiratory lung volume (∆EELV) in response to changes in PEEP (∆PEEP) have not been reported in mechanically ventilated patients with ARDS. The purpose of this study was to determine the utility of measurements of ∆EELV in determining optimal PEEP in ARDS patients. METHODS: Nine patients with ARDS were prospectively recruited. ∆EELV was measured using magnetometers during serial decremental PEEP trials. Changes in PaO2 (∆PaO2) were simultaneously measured. Static respiratory system compliance (CRS), ∆PaO2/∆PEEP, and ∆EELV/∆PEEP were calculated at each level of PEEP. RESULTS: For the group, ∆EELV decreased by 1.09 ± 0.13 L (mean ± SD) as PEEP was reduced from 20 to 0 cm H2O with the greatest changes in ∆EELV occurring over the mid range of the decremental PEEP curve. Optimal values for CRS, ∆EELV/∆PEEP, and ∆PaO2/∆PEEP could be identified for each patient and occurred at PEEP levels ranging from 10 to 17.5 cm H2O. There was a significant correlation (r = 0.712, p = 0.047) between ∆PaO2/∆PEEP and ∆EELV/∆PEEP. CONCLUSIONS: ∆EELV can be measured from a decremental PEEP curve. Since ∆EELV is highly correlated with ∆PaO2, measures of ∆PaO2/∆PEEP may provide a surrogate for measures of ∆EELV/∆PEEP. Combining measures of ∆EELV/∆PEEP with measures of CRS may provide a novel means of determining optimal PEEP in patients with ARDS.

Respiratory dysfunction in multiple sclerosis.

Respiratory dysfunction frequently occurs in patients with advanced multiple sclerosis (MS), and may manifest as acute or chronic respiratory failure, disordered control of breathing, respiratory muscle weakness, sleep disordered breathing, or neurogenic pulmonary edema. The underlying pathophysiology is related to demyelinating plaques involving the brain stem or spinal cord. Respiratory complications such as aspiration, lung infections and respiratory failure are typically seen in patients with long-standing MS. Acute respiratory failure is uncommon and due to newly appearing demyelinating plaques extensively involving areas of the brain stem or spinal cord. Early recognition of MS patients at risk for respiratory complications allows for the timely implementation of care and measures to decrease disease associated morbidity and mortality.

Physiology in Medicine: physiological basis of diaphragmatic dysfunction with abdominal hernias-implications for therapy.

An incisional hernia is a common complication after abdominal surgery. Complaints of dyspnea in this population may be attributed to cardiopulmonary dysfunction or deconditioning. Large abdominal incisional hernias, however, may cause diaphragm dysfunction and result in dyspnea, which is more pronounced when standing (platypnea). The use of an abdominal binder may alleviate platypnea in this population. We discuss the link between diaphragm dysfunction and the lack of abdominal wall integrity and how abdominal wall support partially restores diaphragm function.

Diaphragm ultrasound as a predictor of successful extubation from mechanical ventilation.

INTRODUCTION: The purpose of this study was to evaluate if ultrasound derived measures of diaphragm thickening, rather than diaphragm motion, can be used to predict extubation success or failure. METHODS: Sixty-three mechanically ventilated patients were prospectively recruited. Diaphragm thickness (tdi) was measured in the zone of apposition of the diaphragm to the rib cage using a 7-10 MHz ultrasound transducer. The percent change in tdi between end-expiration and end-inspiration (Δtdi%) was calculated during either spontaneous breathing (SB) or pressure support (PS) weaning trials. A successful extubation was defined as SB for >48 h following endotracheal tube removal. RESULTS: Of the 63 subjects studied, 27 patients were weaned with SB and 36 were weaned with PS. The combined sensitivity and specificity of Δtdi%≥30% for extubation success was 88% and 71%, respectively. The positive predictive value and negative predictive value were 91% and 63%, respectively. The area under the receiver operating characteristic curve was 0.79 for Δtdi%. CONCLUSIONS: Ultrasound measures of diaphragm thickening in the zone of apposition may be useful to predict extubation success or failure during SB or PS trials.

The study design and rationale of the randomized controlled trial: translating COPD guidelines into primary care practice.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating disease associated with significant clinical burden and is estimated to affect 15 million individuals in the US. Although a large number of individuals are diagnosed with COPD, many individuals still remain undiagnosed due to the slow progression of the disorder and lack of recognition of early symptoms. Not only is there under-diagnosis but there is also evidence of sub-optimal evidence-based treatment of those who have COPD. Despite the development of international COPD guidelines, many primary care physicians who care for the majority of patients with COPD are not translating this evidence into effective clinical practice. METHOD/DESIGN: This paper describes the design and rationale for a randomized, cluster design trial (RCT) aimed at translating the COPD evidence-based guidelines into clinical care in primary care practices. During Phase 1, a needs assessment evaluated barriers and facilitators to implementation of COPD guidelines into clinical practice through focus groups of primary care patients and providers. Using formative evaluation and feedback from focus groups, three tools were developed. These include a computerized patient activation tool (an interactive iPad with wireless data transfer to the spirometer); a web-based COPD guideline tool to be used by primary care providers as a decision support tool; and a COPD patient education toolkit to be used by the practice team. During phase II, an RCT will be performed with one year of intervention within 30 primary care practices. The effectiveness of the materials developed in Phase I are being tested in Phase II regarding physician performance of COPD guideline implementation and the improvement in the clinically relevant outcomes (appropriate diagnosis and management of COPD) compared to usual care. We will also examine the use of a patient activation tool - 'MyLungAge' - to prompt patients at risk for or who have COPD to request spirometry confirmation and to request support for smoking cessation if a smoker. DISCUSSION: Using a multi-modal intervention of patient activation and a technology-supported health care provider team, we are testing the effectiveness of this intervention in activating patients and improving physician performance around COPD guideline implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01237561.

Methacholine-induced airway hyper-reactivity phenotypes.

OBJECTIVE: The incorporation of airways conductance/resistance is a rare feature in clinical methacholine challenge test (MCT) protocols, and the majority of pulmonary laboratories rely solely on the spirometric parameters. The importance and interpretation of an MCT demonstrating a significant decline in specific airway conductance specific airway conductance (sGaw), but not forced expiratory volume in one second (FEV(1)), remains undefined. This study sought to elucidate the clinical and physiologic phenotypes of individuals with a ≥40% sGaw decline but <20% FEV(1) change. METHODS: All subjects completed the Asthma Quality of Life Questionnaire (AQLQ), followed by standard MCT, with measurements of sGaw and an additional independent measurement of resistance and reactance by impulse oscillation system (IOS) before and after MCT. RESULTS: Of 201 subjects, 47(23.4%) were in Group 1 (FEV(1) declined by ≥20%), 45(22.4%) were in Group 2 (non-significant FEV(1) drop, sGaw declined ≥40%), and 109(54.2%) were in Group 3 (no significant decline in FEV(1)/sGaw). There was a nearly identical change in all oscillometric parameters and sGaw for Groups 1 and 2 versus Group 3. There were no differences between Groups 1 and 2 in any AQLQ category, and Groups 1 and 2 were statistically different from Group 3. CONCLUSIONS: Our prospective study suggests that patients with a significant sGaw decline alone during MCT are a clinically and physiologically important hyper-reactivity phenotype--whose hyper-reactivity independently was confirmed to be nearly identical to those with an FEV(1) decline. By failing to assess airways conductance/resistance, asthma may be inappropriately "ruled out" in ∼20% of the patients referred for MCT. Based on this, standardized incorporation of body plethysmography and/or IOS to MCT protocols should be considered.