Sarcoidosis-lymphoma syndrome: a diagnostic dilemma.

Sarcoidosis and lymphoma are generally thought of as being two mutually exclusive diseases that need to be considered in the differential diagnosis of patients with hilar/mediastianal lymphadenopathy. However, there are rare patients in whom both of these diseases coexist. These patients constitute a diagnostic challenge because their presentation (ie, clinical symptoms, imaging abnormalities and even pathology) may all be atypical when each individual disease is considered separately. In this report, we describe a patient who presented with such atypical features and was eventually diagnosed as having both sarcoidosis and a B-cell lymphoma with features of splenic marginal zone lymphoma (SMZL) simultaneously. To our knowledge, this is only the second reported case of SMZL and sarcoidosis in the same patient.

Management of idiopathic pulmonary fibrosis: selected case reports.

In 2011, revised international guidelines were issued jointly by the American Thoracic Society, the European Respiratory Society, the Japanese Respiratory Society and the Latin American Thoracic Association, which provide a valuable framework for the diagnosis and management of idiopathic pulmonary fibrosis (IPF). However, due to the complexity of IPF, these guidelines may not comprehensively account for the management of individual IPF patients in clinical practice. We describe three patient cases that were presented and discussed during the 2013 AIR: Advancing IPF Research meeting in Nice, France. These cases highlight the heterogeneity in the presentation, history and clinical course of IPF, together with expert insights regarding the diagnosis and management of IPF in the real-life setting.

Foreign-body aspiration in the adult: presentation and management.

Nonasphyxiating foreign-body aspiration in adults can be difficult to diagnose because the symptoms are nonspecific and chest x-rays may be normal due to organic composition of the foreign bodies. The diagnosis is often made via flexible bronchoscopy; however, debate remains as to whether rigid or flexible bronchoscopy is the optimal method of extraction. The authors describe a patient who was initially referred for assessment of a calcified left mainstem bronchus mass identified only on computed tomography scan of the thorax. The patient underwent flexible bronchoscopy and was discovered to have a bone fragment wedged in the bronchus for a duration of 22 years, which was successfully removed via rigid bronchoscope.

Search for chronic beryllium disease among sarcoidosis patients in Ontario, Canada.

Chronic beryllium disease (CBD) is clinically similar to other granulomatous diseases such as sarcoidosis. It is often misdiagnosed if a thorough occupational history is not taken. When appropriate, a beryllium lymphocyte proliferation tests (BeLPT) need to be performed. We aimed to search for CBD among currently diagnosed pulmonary sarcoidosis patients and to identify the occupations and exposures in Ontario leading to CBD. Questionnaire items included work history and details of possible exposure to beryllium. Participants who provided a history of previous work with metals underwent BeLPTs and an ELISPOT on the basis of having a higher pretest probability of CBD. Among 121 sarcoid patients enrolled, 87 (72%) reported no known previous metal dust or fume exposure, while 34 (28%) had metal exposure, including 17 (14%) with beryllium exposure at work or home. However, none of these 34 who underwent testing had positive test results. Self-reported exposure to beryllium or metals was relatively common in these patients with clinical sarcoidosis, but CBD was not confirmed using blood assays in this population.

Rapid eye movement-related sleep-disordered breathing: influence of age and gender.

BACKGROUND: Sleep-disordered breathing (SDB) occurring during rapid eye movement (REM) sleep occurs more frequently in women than men. We sought to characterize REM SDB prevalence by gender and age to identify factors that could account for this discrepancy. METHODS: Subjects with REM SDB were identified among 2,486 patients referred to a university sleep laboratory with an apnea-hypopnea index (AHI) >or= 5 events per hour. REM SDB was defined as non-REM (NREM) AHI or= 2. Regression analyses were utilized to determine factors associated with REM SDB. RESULTS: REM SDB prevalence was 40.8% in women and 21.0% in men. After adjusting for age and obesity, female sex remained a risk factor for REM SDB (odds ratio, 3.0; 95% confidence interval [CI], 1.8 to 4.2). REM SDB prevalence waned with increasing age in both sexes, such that the odds of having REM SDB fell by 26.7% (95% CI, 15.2 to 38.2%) per decade. REM AHI/NREM AHI decreased with age only in women, falling 10.9% (95% CI, 5.5 to 16.3%) per decade. NREM AHI in women increased the most with age (16.0%; 95% CI, 11.1 to 20.9%) per decade, and least with body mass index (BMI) [13.0%; 9.1 to 16.9%] for every 5-unit BMI increase when compared to REM AHI for women and either index for men. CONCLUSIONS: REM SDB prevalence decreases with age in women as does REM AHI/NREM AHI, perhaps secondary to a disproportionate age-dependent rise in NREM vs REM AHI in women. Younger women may be protected from SDB during NREM sleep, even in the face of obesity. These patterns may reflect age-related decreases in female hormones.

Clinical and immunologic features of an atypical intracranial mycobacterium avium complex (MAC) infection compared with those of pulmonary MAC infections.

Members of the Mycobacterium avium complex (MAC) may cause chronic pulmonary infections in otherwise healthy elderly persons but rarely invade parts of the body outside of the lungs in immunocompetent hosts. We present a case of an isolated intracranial MAC infection in an apparently immunocompetent individual and review previous reports. We studied the T-cell and monocyte responses in healthy volunteers, individuals with a pulmonary MAC infection, and one individual with an isolated intracranial MAC infection. Genomic DNA from the individual with the brain MAC infection was studied for gamma interferon (IFN-gamma) receptor mutations. Individuals with localized pulmonary MAC infections showed increased activation of monocytes and enhanced monocyte and T-cell tumor necrosis factor alpha (TNF-alpha) production in response to lipopolysaccharide and MAC antigens but defects in T-cell IFN-gamma secretion. The individual with an intracranial MAC infection showed a lack of monocyte activation and deficiencies in both monocyte and T-cell TNF-alpha production and monocyte interleukin-12 (IL-12) production but had preserved T-cell IFN-gamma production. Mutations or deletions in the IFN-gamma receptor were not detected in the individual with the intracranial MAC infection. Our data suggest that distinct immune defects characterize two different manifestations of MAC infection. A relative defect in IFN-gamma production in response to MAC may predispose an individual to localized but partially controlled lung disease, whereas defects leading to reduced IL-12 and TNF-alpha production may allow the dissemination of MAC. Further studies delineating the potential role of TNF-alpha in limiting the spread of MAC outside the lung are warranted.

Nocturnal haemodialysis increases pharyngeal size in patients with sleep apnoea and end-stage renal disease.

BACKGROUND: Sleep apnoea is common in patients with end-stage renal disease (ESRD) and is improved by nocturnal haemodialysis (NHD). Recent findings from our laboratory indicate the development of ESRD is associated with pharyngeal narrowing. We hypothesized that NHD increases pharyngeal cross-sectional area and that this is associated with an improvement in sleep apnoea. METHODS: Twenty-four patients (aged 32-68 years), receiving conventional haemodialysis (CHD) (4 h/day, 3 days/week), were recruited for overnight polysomnography and estimation of pharyngeal cross-sectional area at functional residual capacity (FRC) and residual volume (RV). Patients were divided into apnoeic and non-apnoeic groups based on an apnoea-hypopnoea index (AHI) > or = 15/h. Following conversion from CHD to NHD (8 h/night, 3-6 nights/week) all measurements were repeated and apnoeic patients were classified as 'responders' if AHI fell to < 15 events/h. RESULTS: Conversion from CHD to NHD was associated with an increase in pharyngeal cross-sectional area (FRC: 3.29 +/- 0.67 vs 3.39 +/- 0.75 cm(2); RV: 1.91 +/- 0.51 vs 2.13 +/- 0.48 cm(2), P < 0.05), which was not significantly different between groups. Sleep apnoea improved in three patients. CONCLUSIONS: Conversion from CHD to NHD is associated with an increase in pharyngeal cross-sectional area. This may play a role in some patients whose sleep apnoea improves on NHD.

Pleuroparenchymal lung disease secondary to nonoccupational exposure to vermiculite.

An unusual case of pleuroparenchymal lung disease caused by the inhalation of vermiculite dust, presumably containing asbestos fibers is described. The uniqueness of the case lies in the very indirect nature of exposure -- the wife of a factory owner, rather than a worker exposed to asbestos, whose factory manufactured vermiculite. The present case illustrates the importance of taking careful occupational histories of all household members when presented with a patient whose chest radiograph exhibits features consistent with asbestos exposure.

Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial.

BACKGROUND: Treatment of moderate or severe chronic obstructive pulmonary disease (COPD) with combinations of inhaled corticosteroids, long-acting beta-agonists, and long-acting anticholinergic bronchodilators is common but unstudied. OBJECTIVE: To determine whether combining tiotropium with salmeterol or fluticasone-salmeterol improves clinical outcomes in adults with moderate to severe COPD compared with tiotropium alone. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from October 2003 to January 2006. SETTING: 27 academic and community medical centers in Canada. PATIENTS: 449 patients with moderate or severe COPD. INTERVENTION: 1 year of treatment with tiotropium plus placebo, tiotropium plus salmeterol, or tiotropium plus fluticasone-salmeterol. MEASUREMENTS: The primary end point was the proportion of patients who experienced an exacerbation of COPD that required treatment with systemic steroids or antibiotics. RESULTS: The proportion of patients in the tiotropium plus placebo group who experienced an exacerbation (62.8%) did not differ from that in the tiotropium plus salmeterol group (64.8%; difference, -2.0 percentage points [95% CI, -12.8 to 8.8 percentage points]) or in the tiotropium plus fluticasone-salmeterol group (60.0%; difference, 2.8 percentage points [CI, -8.2 to 13.8 percentage points]). In sensitivity analyses, the point estimates and 95% confidence bounds shifted in the direction favoring tiotropium plus salmeterol and tiotropium plus fluticasone-salmeterol. Tiotropium plus fluticasone-salmeterol improved lung function (P = 0.049) and disease-specific quality of life (P = 0.01) and reduced the number of hospitalizations for COPD exacerbation (incidence rate ratio, 0.53 [CI, 0.33 to 0.86]) and all-cause hospitalizations (incidence rate ratio, 0.67 [CI, 0.45 to 0.99]) compared with tiotropium plus placebo. In contrast, tiotropium plus salmeterol did not statistically improve lung function or hospitalization rates compared with tiotropium plus placebo. LIMITATIONS: More than 40% of patients who received tiotropium plus placebo and tiotropium plus salmeterol discontinued therapy prematurely, and many crossed over to treatment with open-label inhaled steroids or long-acting beta-agonists. CONCLUSIONS: Addition of fluticasone-salmeterol to tiotropium therapy did not statistically influence rates of COPD exacerbation but did improve lung function, quality of life, and hospitalization rates in patients with moderate to severe COPD. International Standard Randomised Controlled Trial registration number: ISRCTN29870041.

Review of oral appliances for treatment of sleep-disordered breathing.

Between 1982 and 2006, there were 89 distinct publications dealing with oral appliance therapy involving a total of 3,027 patients, which reported results of sleep studies performed with and without the appliance. These studies, which constitute a very heterogeneous group in terms of methodology and patient population, are reviewed and the results summarized. This review focused on the following outcomes: sleep apnea (i.e. reduction in the apnea/hypopnea index or respiratory disturbance index), ability of oral appliances to reduce snoring, effect of oral appliances on daytime function, comparison of oral appliances with other treatments (continuous positive airway pressure and surgery), side effects, dental changes (overbite and overjet), and long-term compliance. We found that the success rate, defined as the ability of the oral appliances to reduce apnea/hypopnea index to less than 10, is 54%. The response rate, defined as at least 50% reduction in the initial apnea/hypopnea index (although it still remained above 10), is 21%. When only the results of randomized, crossover, placebo-controlled studies are considered, the success and response rates are 50% and 14%, respectively. Snoring was reduced by 45%. In the studies comparing oral appliances to continuous positive airway pressure (CPAP) or to uvulopalatopharyngoplasty (UPPP), an appliance reduced initial AHI by 42%, CPAP reduced it by 75%, and UPPP by 30%. The majority of patients prefer using oral appliance than CPAP. Use of oral appliances improves daytime function somewhat; the Epworth sleepiness score (ESS) dropped from 11.2 to 7.8 in 854 patients. A summary of the follow-up compliance data shows that at 30 months, 56-68% of patients continue to use oral appliance. Side effects are relatively minor but frequent. The most common ones are excessive salivation and teeth discomfort. Efficacy and side effects depend on the type of appliance, degree of protrusion, vertical opening, and other settings. We conclude that oral appliances, although not as effective as CPAP in reducing sleep apnea, snoring, and improving daytime function, have a definite role in the treatment of snoring and sleep apnea.

Acidification of distal esophagus and sleep-related breathing disturbances.

STUDY OBJECTIVES: To investigate whether distal esophageal acidification occurs during sleep in patients suspected of sleep-disordered breathing, and whether such acidification is related to respiratory abnormalities. DESIGN AND PATIENTS: Fourteen middle-aged, snoring men all complaining of daytime sleepiness and suspected of having obstructive sleep apnea. SETTING: Sleep laboratory, Pulmonary Department, Landspitali University Hospital, Reykjavik, Iceland. MEASUREMENTS AND RESULTS: Each patient underwent full nocturnal polysomnography testing, which included continuous monitoring of esophageal pressure (Pes) and pH. We identified all pH events, which were defined as a reduction in esophageal pH of >/= 1.0. During each pH event, the respiratory recordings where examined for the presence of apneas or hypopneas, and Pes was recorded. The data were analyzed to determine the possible relationships between pH events and respiratory events, and between changes in pH and changes in Pes. We found that there were more respiratory events than pH events. The mean (+/- SD) number of apneas and hypopneas per hour of sleep was 33 +/- 22, whereas the mean number of pH events per hour of sleep was 7 +/- 6. Overall, 81% of all pH events were associated with respiratory events. Correlation analysis did not reveal any significant relationship between pH events and the magnitude of Pes or apnea-hypopnea index. CONCLUSIONS: Episodes of esophageal acidification are common in patients with sleep apnea, and are usually associated with respiratory and pressure events. However, changes in pH were independent of the magnitude of the Pes.

Gender differences in sleep apnea: the role of neck circumference.

STUDY OBJECTIVES: To determine whether differences in sleep apnea severity between men and women referred to a sleep clinic are related to the differences in neck circumference (NC). STUDY DESIGN: Case series. SETTING: University hospital sleep disorders clinic. PARTICIPANTS: A total of 3,942 patients (2,753 men and 1,189 women) referred to the sleep clinic. MEASUREMENTS AND RESULTS: All patients underwent nocturnal polysomnography. NC was used as a surrogate measure of upper airway obesity. We found that sleep apnea, defined an the apnea/hypopnea index (AHI) > 10/h, was significantly more frequent (60% vs 32%, chi(2) < 0.0001) and severe (mean +/- SE, 25 +/- 26/h vs 12 +/- 19/h, p < 0.0001) in men than in women. Men had significantly larger NC than women, but the difference became much less pronounced when we normalized NC to body height (0.24 +/- 0.02 vs 0.23 +/- 0.03, p < 0.0001). Men had significantly higher AHI than women even after controlling for age, body mass index (BMI), and neck/height ratio (NHR); analysis of covariance showed that mean AHI was 24.4 +/- 0.4 in men vs 14.8 +/- 0.7 in women (p < 0.0001). This difference persisted even when we matched men and women for NHR and BMI. Finally, multiple regression analysis revealed the following: (1) NHR was the most significant predictor of AHI, accounting for 19% of the variability; and (2) the slope of AHI vs NHR was significantly higher in men than in women. CONCLUSIONS: We conclude the following: (1) the frequency and severity of sleep apnea in the sleep clinic population is greater in men than women, and (2) factors other than NC, age, and BMI must contribute to these gender differences.

Pulmonary function and sleep apnea.

The purpose of this study was to determine whether there is a relationship between pulmonary function measured during wakefulness and sleep apnea. We prospectively studied 1296 patients, who were free of any lung disease, referred to our sleep clinic for evaluation of possible sleep apnea. All patients had in-hospital nocturnal polysomnography and pulmonary function measurements, which included flow-volume curve, body plethysmography, and single-breath diffusing capacity for carbon monoxide. The results were analyzed by comparing pulmonary function data between four groups of patients, grouped according to apnea severity as reflected by their apnea/hypopnea index: nonapneics (apnea-hypopnea index 50). Analysis of covariance demonstrated no difference in any of the pulmonary function parameters between the four groups, after adjusting for age, body mass index, or weight as the covariate. We conclude that in nonsmoking patients without lung disease, sleep apnea is unrelated to pulmonary function measured during wakefulness.