Mordechai Yigla

Difficult-to-control asthma and obstructive sleep apnea.

This study tested the hypothesis that asthma can promote obstructive sleep apnea (OSA) by looking at the prevalence of OSA among patients with difficult‐to‐control asthma receiving long‐term oral corticosteroid (CS) therapy and examined some possible etiological factors. The study design was a prospective cohort study and was conducted in the pulmonary outpatient clinic of a tertiary care center in Haifa, Israel. Twenty‐two consecutive patients with severe unstable asthma, 14 on continuous and 8 on bursts of oral CS, in addition to their standard therapy for a mean of 8.9 ± 3.3 years, underwent a night polysomnography in a sleep laboratory regardless of sleep complaints. A standard questionnaire was completed upon attending the sleep laboratory. The OSA was defined as respiratory disturbance index (RDI) of ≥ 5 and typical complaints. The correlation between RDI to asthma and morphometric parameters was tested. All but one patient had OSA [95.5% prevalence], with mean RDI of 17.7 ± 2.5. The RDI values were significantly higher in the continuous CS therapy subgroup (21.4 ± 3.4 vs. 11.1 ± 1.6, p < 0.05]. The study group had above normal neck circumferences and body mass index. The former increased by 12.1% ± 3.1% to 29.8% ± 1% during the oral CS therapy interval but had no significant effect on RDI as a covariant. This study showed an unexpectedly high prevalence of OSA among patients with unstable asthma receiving long‐term chronic or frequent burst of oral CS therapy. It may be assumed that prolonged and especially continuous oral CS therapy in asthma increases airway collapsibility.

Pulmonary hypertension is an independent predictor of mortality in hemodialysis patients

Pulmonary hypertension in patients with end-stage renal disease on hemodialysis is a newly described entity. To determine its impact, we measured selected clinical variables in the survival of 127 hemodialysis patients. Overall, pulmonary hypertension was found in 37 of these patients; it was already prevalent in 17 of them before initiation of dialysis and was associated with severe cardiac dysfunction. In the other 20 it developed after dialysis began, without obvious cause. These two subgroups of patients had similar survival curves, which were significantly worse in comparison to those without pulmonary hypertension. Following the initiation of hemodialysis, 20 patients with otherwise matched clinical variables survived significantly longer than the 20 who developed pulmonary hypertension after dialysis began. With univariate analysis, significant hazard ratios were found for age at onset of hemodialysis therapy (1.7), valvular diseases (1.8), pulmonary hypertension prevalence before hemodialysis (3.6) and incident after hemodialysis (2.4) for predicting mortality. In a multivariable Cox proportional hazard model, the development of pulmonary hypertension both before and after initiation of hemodialysis had significantly increased odds ratios and remained an independent predictor of mortality. Our study shows the incidence of pulmonary hypertension, after initiation of hemodialysis therapy, is a strong independent predictor of mortality nearly equal to that associated with long-standing severe cardiac abnormalities.

Pulmonary Hypertension in Hemodialysis Patients: An Unrecognized Threat

Pulmonary hypertension (PH) is a progressive, fatal pulmonary circulatory disease that accompanies many conditions (including left to right side shunt) with compensatory elevated cardiac output. PH also complicates chronic hemodialysis (HD) therapy immediately after the creation of an arteriovenous (AV) access, even before starting HD therapy. It tends to regress after temporary AV access closure and after successful kidney transplantation. Affected patients have significantly higher cardiac output. This syndrome is associated with a statistically significant survival disadvantage. The laboratory hallmark of this syndrome is reduced basal and stimulatory nitric oxide (NO) levels. It appears that patients with end‐stage renal disease (ESRD) acquire endothelial dysfunction that reduces the ability of their pulmonary vessels to accommodate the AV access‐mediated elevated cardiac output, exacerbating the PH. Doppler echocardiographic screening of ESRD patients scheduled for HD therapy for the occurrence of PH is indicated. Early diagnosis enables timely intervention, currently limited to changing dialysis modality or referring for kidney transplantation.

Pulmonary hypertension in chronic dialysis patients with arteriovenous fistula: pathogenesis and therapeutic prospective

Purpose of reviewEnd-stage renal disease patients receiving chronic haemodialysis via arteriovenous access often develop various cardiovascular complications, including vascular calcification, cardiac-vascular calcification and atherosclerotic coronary disease. This review describes recently published studies that demonstrate a high incidence of pulmonary hypertension among patients with end-stage renal disease receiving long-term haemodialysis via a surgical arteriovenous fistula. Both end-stage renal disease and long-term haemodialysis via arteriovenous fistula may be involved in the pathogenesis of pulmonary hypertension by affecting pulmonary vascular resistance and cardiac output. Recent findingsMorbidity and mortality from cardiovascular disease are greatly increased in patients on maintenance haemodialysis therapy. Using Doppler echocardiography, we found a significant increase in cardiac output in 40% of chronic haemodialysis patients, probably related to the large arteriovenous access or altered vascular resistance as a result of the local vascular tone and function expressed by the imbalance between vasodilators such as nitric oxide, and vasoconstrictors such as endothelin-1. SummaryWe propose different potential mechanisms as explanations for the development of pulmonary hypertension. Hormonal and metabolic derangement associated with end-stage renal disease might lead to pulmonary arterial vasoconstriction and an increase in pulmonary vascular resistance. Pulmonary arterial pressure may be further increased by high cardiac output resulting from the arteriole–venous access itself, worsened by commonly occurring anaemia and fluid overload.

Nosocomial outbreak of Legionella pneumophila serogroup 3 pneumonia in a new bone marrow transplant unit: evaluation, treatment and control

A nosocomial outbreak of pneumonia caused by Legionella pneumophila serogroup 3 occurred in four patients following hematopoietic stem cell transplantation (HSCT) in a new bone marrow transplantation (BMT) unit during a 2 week period. The causative organism was recovered from the water supply system to the same unit just before the outbreak. Nineteen other BMT patients were hospitalized in the same unit at the same time, giving a frequency of proven infection of 4/23 = 17%. Immediately after recognition of the outbreak, use of tap water was forbidden, humidifiers were disconnected, and ciprofloxacin prophylaxis was started for all patients in the unit, until decontamination of the water was achieved. No other cases were detected. In conclusion, contamination of the hospital water supply system with legionella carries a high risk for legionella pneumonia among BMT patients. Early recognition of the outbreak, immediate restrictions of water use, antibiotic prophylaxis for all non-infected patients, and water decontamination, successfully terminated the outbreak.

Non-Hodgkin's lymphoma presenting as an endobronchial tumor: Report of eight cases and literature review

Non‐Hodgkins lymphoma (NHL) involving the endobronchial tree is uncommon, and the initial presentation of NHL as an endobronchial tumor is extremely rare. In a series of 441 patients with newly diagnosed non‐Hodgkins lymphoma over a 7‐year period, we reviewed the clinical features of eight patients who presented with an endobronchial tumor. All patients had local pulmonary disease without extrathoracic involvement. The major presenting symptoms were dyspnea, chest pain, cough, and hoarseness. None of the patients had systemic symptoms. Radiographs revealed lobar collapse in all cases. Five patients had mediastinal masses and three had isolated endobronchial lesions. Although MALT lymphoma is the most common primary pulmonary lymphoma, it was present in only one of our patients, while seven patients had aggressive lymphoma. All patients received chemotherapy. Six of the eight patients responded favorably to treatment with complete remission. The prognosis of patients with isolated endobronchial lymphoma is not worse than other local presentations of lymphoma. Bronchoscopic examination with biopsy is essential to differentiate these lesions from primary bronchongenic carcinoma. Am. J. Hematol., 2008.

Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy

BackgroundLeflunomide (LEF) is indicated in adults for the treatment of active rheumatoid arthritis (RA). LEF inhibits dehydroorotate dehydrogenase, a key enzyme of the pyrimidine synthesis in activated lymphocytes. Among rare adverse effects, fatal interstitial lung disease has been recently reported during treatment of RA with LEF in Japan. Clinical trials outside Japan do not suggest that LEF causes an excess of pulmonary adverse effects. Development and increase of peripheral rheumatoid nodules in typical sites of RA patients following LEF therapy has been recently reported.ObjectivesTwo cases with new and accelerated development of rheumatoid lung nodulosis during LEF therapy were described in this study.MethodsLEF treatment was administered to two male patients (77 and 66 years old) with long-standing active seropositive nodular RA with failure of multiple second line drugs and without lung involvement. Clinical and laboratory assessment using the American College of Rheumatology response criteria, chest computed tomography (CT), quantification of serum rheumatoid factor (RF), and monocyte count of peripheral blood along with routine laboratory follow up were performed on both patients before and during therapy. In case 1, a bone scan was performed due to sustained limbs pain. Open lung biopsy was performed in case 1 and core lung biopsy in case 2.ResultsBoth patients achieved full clinical remission during 2 months of LEF therapy. In case 1, the first complaints were limbs pain after 10 months of treatment associated with intensive bone uptake on a bone scan consistent with hypertrophic pulmonary osteopathy. Productive cough developed after 3 months of the therapy in case 2. Initially, these complaints were not attributed to therapy. New lung disease was present on CT with cherry-like progressive cavitary nodules, predominantly involving the basal segments of the right lung. The first lung lesions were found by CT 13 months (case 1) and 7 months (case 2) after the beginning of therapy and were erroneously related to bronchiectasia in case 2. In both cases, the lung biopsy showed necrosis surrounded by epithelioid mononuclear inflammation with giant cells, consistent with rheumatoid lung node. The time that elapsed between the beginning of the first symptoms to LEF discontinuation was very long: 13 months in case 1 and 24 months in case 2. Discontinuation of LEF therapy was followed by an arrest in growth of lung nodules, resolution of limb pain, and gradual improvement of bone scan. A significant decrease of monocyte count and RF level in peripheral blood was observed during LEF therapy in both cases.ConclusionFor the first time, we described rheumatoid lung nodulosis as complication of successful LEF therapy for RA. Hypertrophic pulmonary osteopathy with severe limbs pain and dry cough were the first manifestations of the lung nodulosis. Monocytopenia during LEF therapy is proposed to be involved in pathogenesis of this rare complication of LEF therapy.

Predictors of long‐term survival in elderly patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease

Background and objective:  There is a paucity of survival data regarding the prognosis of elderly patients following acute exacerbations of COPD (AECOPD). We undertook a study to examine long‐term mortality rates and to identify clinical and laboratory predictors of these outcomes.

Cardiac Troponin-I Predicts Long-Term Mortality in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease patients are at increased risk for mortality, particularly from cardiovascular conditions. Acute exacerbation increases heart burden and may lead to release of troponin I. This study investigates the long-term prognostic value of elevated troponin I detected during acute exacerbation of chronic obstructive pulmonary disease. The records of 182 patients with acute exacerbation in whom troponin I levels were sampled during their hospitalization were reviewed retrospectively. Receiver operator curve was used to determine the cut-off level for troponin I that discriminated survivors and non-survivors, and predictors for all-cause mortality were tested in a multivariate analysis. The results showed that, during a mean observation time of 50.1 ± 45.6 months, 66 (36.3%) patients died, providing 1, and 3-year survival rates of 84%, and 54%, respectively. Troponin I levels were significantly higher in non-survivors compared with survivors, mean troponin I ± SD in μ g· L−1: 1.35 ± 3.17 vs. 0.53 ± 2.08, respectively, p = 0.0033. ROC curve analysis identified troponin I > 0.03 μ g· L−1 as the optimal cut-off level for prediction of mortality. Kaplan-Meier survival analysis revealed that the probability of survival was significantly lower in patients with troponin I > 0.03 μ g· L−1 (log-rank test p = 0.0058). On multivariate analysis, only ischemic heart disease (HR = 2.335, p = 0.0017) and troponin I level (HR = 1.31541, p = 0.2513) were independent predictors of mortality. In conclusion, it was found that a mildly elevated troponin I level measured in patients with chronic obstructive pulmonary disease during acute exacerbation is a strong independent predictor of mortality following discharge.

Pulmonary Arteries Involvement in Takayasu's Arteritis: Two Cases and Literature Review

OBJECTIVES To review pulmonary arteritis (PA) complicated by pulmonary arterial hypertension (PAH) in Takayasus arteritis (TA). METHODS Two cases of PA and PAH in TA patients and similar cases published in the Medline database from 1975 to 2009 were reviewed. RESULTS Forty-six cases (females 89.1%, Asians 65%, mean age 34.6 years) were analyzed, 42.2% of which had PAH. Isolated PA was reported in 31.8%. Respiratory symptoms were presented as dyspnea (75.5%), chest pain (48.9%), hemoptysis (42.2%), and cough (17.7%). Hypertension, vascular bruits, and diminished/absent pulses were reported in 48.9% of patients. A diagnosis of PA was based on abnormal uptake on pulmonary perfusion scan and a finding of stenosis, narrowing, occlusion, and irregularity on computed tomography or magnetic resonance imaging, and/or pulmonary angiography. Patients were treated with glucocorticoids (77.5%), disease-modified antirheumatic drugs (35%), and warfarin (20%); only a few were treated with biological agents. Vascular procedures were performed in 52.5% of cases, on pulmonary arteries in 37.5% with good results. The outcome was death in 20.5% of PA patient and 33.3% in PAH patients. CONCLUSIONS TA may be complicated by life-threatening PA and PAH. Clinical signs are not specific and may be masked by involvement of the aorta and its branches. Treatment with glucocorticoids and disease-modified antirheumatic drugs has only partial effect, which may be intensified by biological agents. Invasive procedures on pulmonary arteries may be a complementary option. PA and PAH in TA patients should be recognized early and treated promptly for prevention of irreversible vascular damage.