Sachin R. Pendharkar

The clinical significance of exhaled nitric oxide in asthma

Asthma is an inflammatory disease of the airways, for which many therapeutic options are available. Guidelines for the management of asthma suggest a stepwise approach to pharmacotherapy based on assessment of asthma severity and control. However, the assessment of asthma control presently relies on surrogate measures, such as the frequency of symptoms or the frequency of use of short-acting beta2-adrenergic agonists. There is no simple, noninvasive technique for the assessment of severity of actual airway inflammation in asthma. The collection and analysis of nitric oxide (NO) levels in exhaled breath has recently become feasible in humans. Based on increased exhaled NO (eNO) levels in patients with asthma, eNO analysis has been proposed as a novel, noninvasive approach to the assessment and monitoring of airway inflammation, and as a basis for adjustments in asthma therapy. In the present paper, the relationship of elevated eNO levels in asthma with inflammatory, physiological and clinical markers of asthma in adults was reviewed. Use of eNO is a promising tool for diagnosing asthma, for monitoring asthma control and for guiding optimal anti-inflammatory asthma therapy. However, because of many unresolved questions, eNO cannot be recommended at present for routine clinical management of adults with asthma.

Prevalence of Sleep-disordered Breathing in Obese Patients with Chronic Hypoxemia. A Cross-Sectional Study

RATIONALE Hypoxemia in obese patients is likely to be associated with a high prevalence of sleep-disordered breathing. Supplemental oxygen is commonly used to treat chronic hypoxemia but carries some risk in obese individuals due to unrecognized comorbid obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). OBJECTIVES The first step in the estimation of this risk is to determine the prevalence of OSA and OHS in obese individuals with chronic, awake hypoxemia. METHODS A single-center retrospective cohort study was performed to assess the prevalence and severity of OSA and OHS among obese individuals with hypoxemia. One hundred eighty-four individuals underwent arterial blood gas testing and polysomnography. One hundred fifty-eight of these individuals also had spirometry. MEASUREMENTS AND MAIN RESULTS The prevalence of OSA was 80%, and the prevalence of OHS was 51%. Chronic obstructive pulmonary disease (COPD) was confirmed by spirometry in 49% of the cohort, and OSA was found in 69% of those individuals. The severity of hypoxemia in this cohort was not statistically related to COPD, OSA, or OHS. CONCLUSIONS OSA and OHS are highly prevalent in obese patients with chronic awake hypoxemia, and OSA frequently coexists with COPD. Evaluation of chronic, awake hypoxemia solely based on arterial blood gas measurements and pulmonary function testing is not sufficient to identify OSA and OHS. Further diagnostic sleep testing should be performed to identify those who could benefit from alternative therapies and to avoid potential harm from treatment with supplemental oxygen alone.

Using patient flow simulation to improve access at a multidisciplinary sleep centre

The lack of timely access to diagnosis and treatment for sleep disorders is well described, but little attention has been paid to understanding how multiple system constraints contribute to long waiting times. The objectives of this study were to identify system constraints leading to long waiting times at a multidisciplinary sleep centre, and to use patient flow simulation modelling to test solutions that could improve access. Discrete‐event simulation models of patient flow were constructed using historical data from 150 patients referred to the sleep centre, and used to both examine reasons for access delays and to test alternative system configurations that were predicted by administrators to reduce waiting times. Four possible solutions were modelled and compared with baseline, including addition of capacity to different areas at the sleep centre and elimination of prioritization by urgency. Within the model, adding physician capacity improved time from patient referral to initial physician appointment, but worsened time from polysomnography requisition to test completion, and had no effect on time from patient referral to treatment initiation. Adding respiratory therapist did not improve model performance compared with baseline. Eliminating triage prioritization worsened time to physician assessment and treatment initiation for urgent patients without improving waiting times overall. This study demonstrates that discrete‐event simulation can identify multiple constraints in access‐limited healthcare systems and allow suggested solutions to be tested before implementation. The model of this sleep centre predicted that investments in capacity expansion proposed by administrators would not reduce the time to a clinically meaningful patient outcome.

Diagnosis and treatment of obstructive sleep apnea in adults

KEY POINTS Obstructive sleep apnea (OSA) is characterized by recurring episodes of cessation (apnea) or reduction (hypopnea) in airflow during sleep caused by obstruction of the upper airway. In recent population-based studies, the estimated prevalence of moderate to severe sleep-disordered

Treatment of Sleep Disordered Breathing Liberates Obese Hypoxemic Patients from Oxygen

Background Obese hypoxemic patients have a high prevalence of sleep disordered breathing (SDB). It is unclear to what extent treatment of SDB can improve daytime hypoxemia. Methods We performed a retrospective cohort study of obese hypoxemic individuals, all of whom underwent polysomnography, arterial blood gas analysis, and subsequent initiation of positive airway pressure (PAP) therapy for SDB. Patients were followed for one year for change in partial pressure of arterial oxygen and the need for supplemental oxygen. Results One hundred and seventeen patients were treated with nocturnal PAP and had follow-up available. Adherence to PAP was satisfactory in 60%, and was associated with a significant improvement in daytime hypoxemia and hypercapnea; 56% of these patients were able to discontinue supplemental oxygen. Adherence to PAP therapy and the baseline severity of OSA predicted improvement in hypoxemia, but only adherence to PAP therapy predicted liberation from supplemental oxygen. Conclusions The identification and treatment of SDB in obese hypoxemic patients improves daytime hypoxemia. It is important to identify SDB in these patients, since supplemental oxygen can frequently be discontinued following treatment with PAP therapy.

Granulomatous Pneumocystis Jiroveci Pneumonia Associated with Immune Reconstituted HIV

Pneumocystis jiroveci pneumonia uncommonly presents with pulmonary nodules and granulomatous inflammation. An unusual case of granulomatous P jiroveci pneumonia in an HIV patient with a CD4(+) lymphocyte count of greater than 200 cells⁄mm(3), occurring in the context of immune reconstitution with highly active antiretroviral therapy, is described. The case highlights the importance of establishing this diagnosis to institute appropriate therapy.

Validity of administrative data for identification of obstructive sleep apnea

Obstructive sleep apnea (OSA) is a common condition associated with significant morbidity and health‐care utilization. We determined the validity of an algorithm derived from administrative data for identifying OSA using the respiratory disturbance index (RDI) as the reference standard. We conducted a retrospective cohort study of adults in Alberta, Canada referred for facility and community‐based sleep diagnostic testing between July 2005 and August 2007. Validity indices were estimated for several case definitions of OSA derived from outpatient physician billing claims and hospital discharge codes. For each algorithm, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated against several reference standards for OSA (RDI ≥ 5 h−1, RDI ≥ 15 h−1 or RDI ≥ 30 h−1). For the 2149 patients included in the study, an algorithm requiring one hospital discharge code or two outpatient billing claims identifying OSA in a 2‐year period had a sensitivity of 24.1%, specificity of 67.8%, PPV of 74.8% and NPV of 18.3% (reference standard RDI ≥ 5 h−1). When comorbidities were included in the case definition, the specificity was 90.5% and PPV was 83.3% (reference standard RDI ≥ 5 h−1). Similar findings were observed using RDI ≥ 15 h−1 and ≥30 h−1 as the reference standard. We identify a claims‐based algorithm that identifies OSA with a high degree of specificity in patients referred for sleep diagnostic testing. This validated algorithm has a good PPV and may be useful when identifying patients with OSA for population studies within a single‐payer health‐care system.

Supplemental Oxygen in Interstitial Lung Disease: An Art in Need of Science

&NA; Interstitial lung disease (ILD) comprises a large and heterogeneous group of disorders that often lead to progressive fibrosis and premature death. Oxygen supplementation is typically used in patients with advanced lung disease with resting hypoxemia; however, there is a paucity of evidence guiding the use of supplemental oxygen in ILD, and significant heterogeneity in clinical practice. It remains unclear whether supplemental oxygen improves clinically meaningful outcomes, and the role of ambulatory oxygen supplementation in isolated exertional hypoxemia is particularly controversial. In some regions, the lack of robust data creates barriers to funding support and access to supplemental oxygen for patients with ILD. Further research into the role of oxygen supplementation is needed to optimize the comprehensive care of this patient population.

Healthcare Use in Individuals with Obesity and Chronic Hypoxemia Treated for Sleep Disordered Breathing.

STUDY OBJECTIVES To determine if treatment of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) among patients with chronic hypoxemia is associated with reduced healthcare utilization. METHODS We performed a retrospective cohort study of 129 obese, hypoxemic patients who underwent polysomnography and were prescribed positive airway pressure (PAP) therapy. During a 2-year follow-up period we examined the associations between adherence to PAP therapy and rates of hospitalization, emergency room (ER) visits, and outpatient visits. RESULTS Severe OSA and OHS were common, as were hypertension, cardiovascular, and pulmonary disease. Forty-nine percent of patients were adherent with PAP therapy. Compared to patients who were not adherent to PAP therapy, adherent patients had significantly lower rates of all-cause hospitalization (incident rate ratio [IRR]:0.55, 95% CI 0.33, 0.93) after adjustment for age, sex and hospitalisation rates prior to treatment. Adjustment for additional comorbidities attenuated this association (IRR: 0.61, 95% CI 0.35, 1.06). Adherence with PAP therapy was associated with lower odds of frequent hospitalization (odds ratio 0.23, 95% CI 0.07, 0.73). There were no significant differences in the rates of ER or outpatient visits between adherent and non-adherent patients. CONCLUSIONS Adherence with PAP treatment in patients with chronic hypoxemia and chronic medical disorders is associated with reduced rates of hospitalization, which has significant benefit both for patients and the healthcare system.

An observational study of the effectiveness of alternative care providers in the management of obstructive sleep apnea.

Alternative care providers have been proposed as a substitute for physician‐based management of obstructive sleep apnea. The purpose of this study was to describe the clinical course of patients with a new diagnosis of obstructive sleep apnea who were treated with continuous positive airway pressure and followed by alternative care providers at a tertiary care sleep clinic. It was hypothesized that care by alternative care providers would result in improvement of daytime sleepiness and satisfactory treatment adherence, and that a specific number of follow‐up visits could be identified after which clinical outcomes no longer improved. The Epworth Sleepiness Scale score was measured for each patient at baseline and at each alternative care provider visit. Patients were discharged when they demonstrated a significant improvement in sleepiness and were adherent to therapy. The Epworth Sleepiness Scale score decreased by 3.9 points from baseline to discharge. Patients with three or more visits required more follow‐up time to achieve the same clinical improvement as those with only two visits. Continuous positive airway pressure adherence was comparable to previous studies of physician‐led care and improved with ongoing alternative care provider follow‐up. The current results suggest that clinical care by alternative care providers leads to continued improvements in sleepiness in patients with obstructive sleep apnea who are treated with continuous positive airway pressure, and that a minority of patients require longer follow‐up to achieve a satisfactory clinical response to therapy.