Perspectives on Using Race in Pulmonary Function Testing: A National Survey Fellows and Program Directors.

BACKGROUND: Pulmonary function tests (PFTs) have historically used race-specific prediction equations. The recent American Thoracic Society guidelines recommend the use of a race-neutral approach in prediction equations. There are limited studies centering the opinions of practicing pulmonologists on the use of race in spirometry. Provider opinion will impact adoption of the new guideline. The aim of this study was to ascertain the beliefs of academic pulmonary and critical care providers regarding the use of race as a variable in spirometry prediction equations. METHODS: We report data from 151 open-ended responses from a voluntary, nationwide survey (distributed by the Association of Pulmonary Critical Care Medicine Program Directors) of academic pulmonary and critical care providers regarding the use of race in PFT prediction equations. Responses were coded using inductive and deductive methods, and a thematic content analysis was conducted. RESULTS: There was a balanced distribution of opinions among respondents supporting, opposing, or being unsure about the incorporation of race in spirometry prediction equations. Responses demonstrated a wide array of understanding related to the concept and definition of race and its relationship to physiology. CONCLUSIONS: There was no consensus among providers regarding the use of race in spirometry prediction equations. Concepts of race having biologic implications persist among pulmonary providers and will likely affect the uptake of the Global Lung Function Initiative per the American Thoracic Society guidelines.

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.

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.

Pulmonary Function Testing in Neuromuscular and Chest Wall Disorders.

Neuromuscular and chest wall disorders frequently compromise pulmonary function, and thorough respiratory evaluation often can assist in diagnosis, risk assessment, and prognosis. Because many of these disorders can be progressive, serial assessments are necessary to best define a trajectory of impairment (or improvement with therapy). This article covers the major respiratory testing modalities available in the evaluation of these patients, emphasizing both the benefits and shortcomings of each approach. Most 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.

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.

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.

New developments in the assessment of COPD: early diagnosis is key.

Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world, and its associated health burdens and costs are mounting. Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively fruitless effort, since treatments other than already ubiquitous smoking-cessation efforts were unlikely to alter its course. However, there is strong evidence to suggest that the majority of patients with objective COPD are not aware of their condition, and this leads to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment. Novel methods of diagnostic testing, community health programs, and primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages - where recent evidence suggests a rapid decline in lung function occurs and may be prevented if acted upon. This review explores the evidence to support the efforts to justify programs aimed at early diagnosis, alternative diagnostic strategies that may augment traditional spirometry, therapeutic modalities that could potentially be used in the future to alter early lung-function decline, and emphasizes the necessary cooperative role that physicians, patients, communities, and governments need to play to realize the significant health impact that stands to be gained.

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.

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.

The use of thrombolytic therapy in pregnancy.

The relative hypercoagulable state of pregnancy leads to an increased risk of thrombotic complications, of which some may be life-threatening or medically devastating. In the non-pregnant patient, the current guidelines suggest thrombolysis as the primary treatment in acute ischemic stroke, myocardial infarction when percutaneous intervention is unavailable, certain cases of mechanical valve thrombosis, and pulmonary embolism with hemodynamic compromise or shock. Given that clinical trial data regarding thrombolytic use in pregnant women are absent due to exclusion, the goal of this review is to summarize the available published data regarding the use of thrombolytic agents and subsequent outcomes and complications in pregnant women. Overall, the use of thrombolytic agents in pregnancy is associated with a relatively low reported complication rate, especially given the severe medical conditions for which they are indicated. The data would suggest that thrombolysis should be considered for appropriate indications similar to that of non-pregnant patients. However, caution should be exercised when drawing conclusions regarding maternal and fetal safety, given the lack of controlled clinical trials including pregnant women and the nature of the weak evidence level of the cumulative data presented in this review.

Initial risk assessment for pulmonary hypertension in patients with COPD.

BACKGROUND: Pulmonary hypertension (PH) is a comorbidity associated with increased mortality in chronic obstructive pulmonary disease (COPD) patients. It is not known which clinical markers are predictive of PH in COPD. The goal of this study was to develop a clinical tool to identify patients who should be sent for initial screening with echocardiography. METHODS: Of 127 patients screened, 94 primary-care patients with COPD were enrolled. All underwent full pulmonary function testing, 6-minute walk distance (6MWD), exercise oximetry, Saint George's Respiratory Questionnaire, and transthoracic echocardiography. Eighty-six patients had measurable pulmonary artery pressures (PAP) on echocardiography. Elevated PAP was defined as a systolic PAP > 35 mmHg. RESULTS: Pre- and post-bronchodilator FEV(1) (P = 0.04 and P = 0.03, respectively), exercise oxyhemoglobin desaturation (P = 0.003), and 6MWD (P = 0.004) were associated with elevated PAP on univariate analysis. Diffusion capacity was lower but did not reach statistical significance (P = 0.07). In multivariate analysis, statistically significant independent variables were >3% decrease in exercise oxyhemoglobin saturation and decline in prebronchodilator FEV(1) (P = 0.01 and P = 0.04, respectively). A composite prediction model was developed that assigned one point for each of the following: age > 55 years, oxyhemoglobin desaturation > 3%, prebronchodilator FEV(1) < 50% predicted, and 6MWD < 1175 ft. Prevalence rates of elevated PAP were 32% for a score of 0-1 (low risk), 68% for a score of 2 (moderate risk), and 78% for a score of 3-4 (high risk). The composite score exhibited a strong trend with elevated PAP prevalence (Cochrane-Armitage trend statistic P = 0.001). CONCLUSION: A simple prediction tool using routine office-based parameters can be used to identify COPD patients at high risk for elevated PAP and initiate the first step in screening for PH with echocardiography. It is important that right heart catheterization be performed to confirm the diagnosis and guide treatment decisions.

Treatment options for cystic fibrosis: state of the art and future perspectives.

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by chronic lung and sinus disease, impaired mucociliary clearance (leading to recurrent pulmonary infection), pancreatic insufficiency, elevated sweat chloride levels and male infertility. Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel in the plasma membrane of epithelial cells lining the lung, pancreas, liver, intestines, sweat duct, and the epididymis. Genetic mutations in CFTR affect its synthesis, processing, and transport to the plasma membrane and/or impede its function as a chloride channel and conductance regulator. Research is proceeding on multiple fronts including inhalational agents, anti-inflammatory treatments, and pancreatic replacement therapies. Furthermore, improved understanding of the molecular mechanisms that lead to CFTR dysfunction has stimulated the design of therapeutic strategies aimed at restoration of CFTR function, or "protein repair therapy". Recent clinical trials have shown these interventions have the ability to restore some level of CFTR function in vivo. This review will provide an overview of recent clinical trials that investigate new therapeutic approaches in CF designed to treat chronic respiratory infection, reduce inflammation, and improve pancreatic enzyme supplementation as well as trials addressing the greatest therapeutic challenge--restoring the function of the CFTR protein.

The role of natriuretic peptides in inflammation and immunity.

The natriuretic peptides (NPs) are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of effects throughout the body. There is growing realization that NP actions go far beyond volume and blood pressure homeostasis. Their pleiotropic effects include a significant role in regulating the immune system. Localization of NP receptors in various immune organs as well as in modulation of inflammation in vascular disease supports this hypothesis. Immune cells, including macrophages, dendritic cells, and T lymphocytes, express receptors for NPs. NPs are also involved in polarizing the immune response to allergens. NPs play an important role in shaping the early immune response to environmental antigens and appear to play a critical role in the interaction between cells of the innate and adaptive immune systems. The recent explosion of basic and clinical research has resulted in improved understanding of their molecular structure. This has facilitated development of chimeric forms of NPs as well as more convenient routes of administration. Thus, the NPs and their receptors could be exploited to develop therapeutics for the inflammatory and immune responses in wide range of diseases. Also discussed are several patents regarding NPs in the present review.

Using serial severity scores to predict death in ICU patients: a validation study and review of the literature.

PURPOSE OF REVIEW: The present study describes the use of serial severity scores to predict death in ICU patients and compares the results with previously published literature on this topic. RECENT FINDINGS: Predicting mortality in critically ill patients has tremendous significance and methods to do so accurately have been studied for decades. The ability to accurately predict death impacts medical therapies, triaging, end-of-life care, and many other aspects of ICU care. There are many methods in existence to help physicians predict mortality, but most are not very accurate on an individual basis. The main tools available are severity scores, published outcomes data, and personal experience and all of them have significant limitations. One strategy that has been shown to be effective in accurately predicting death is to use serial severity scoring during the patient's ICU admission. Recently, a retrospective study done on a large cohort of ICU patients at a single institution showed very high specificity in predicting death by using serial acute physiology, age, and chronic health evaluation (APACHE III) scores on days 1 and 3. The authors of this article sought to validate this study in a different institution using a slightly different model that was easier to use and might increase sensitivity. The results of this small study are presented with a review of the literature on the use of serial scores to predict death in ICU patients. SUMMARY: Over the years multiple studies have shown that systems using serial severity scores can predict death in ICU patients with very high but not perfect accuracy. The clinical use of these systems remains low however and ultimately their main utility may be in research.