Thierry Rochat

New bioelectrical impedance formula for patients with respiratory insufficiency: comparison to dual-energy X-ray absorptiometry.

Malnutrition in patients with severe respiratory insufficiency can lead to severe complications, justifying the use of objective nutritional assessment techniques, such as bioelectrical impedance analysis (BIA), which is an easy, noninvasive method of measuring body composition. The purpose of this study was to develop, and validate against dual-energy X-ray absorptiometry (DXA), a BIA formula to predict fat-free mass (FFM) specific for patients with chronic severe respiratory insufficiency. Seventy-five ambulatory patients (15 females and 60 males) with severe chronic respiratory insufficiency (obstructive and restrictive) aged 63.6+/-19.2 yrs (mean+/-SD), in a stable pulmonary and cardiac condition for > or = 2 months, were measured simultaneously with BIA and DXA. Patients younger than 45 yrs of age and with a body mass index > or = 32 kg x m(-2) were excluded. The best-fitting multiple regression equation to predict FFM = -6.06 +/- (height x 0.283) +/- (weight x 0.207) - (resistance x 0.024) +/- (sex (males=1, females=0) x 4.036), gave a correlation coefficient of r=0.952, slope+/-SEM 0.902+/-0.034, standard error of the estimate 1.670, and p<0.0001. The mean difference for FFM was 0.2+/-2.3 kg (mean+/-SD) and percentage fat mass was -0.7+/-3.8%. These results suggest that the bioelectrical impedance analysis formula specific to patients with severe respiratory insufficiency give a better correlation and smaller mean differences than 12 different bioelectrical impedance analysis formulae described in the medical literature. A prediction equation, validated against dual-energy X-ray absorptiometry and based on subjects with similar clinical characteristics, is more applicable to the patients with respiratory insufficiency than a formula developed for healthy subjects.

Quantitative scoring of an interferon-γ assay for differentiating active from latent tuberculosis

The aim of this study was to assess the contribution of an interferon-γ release assay (T-SPOT.TB) to the differentiation of active tuberculosis (TB) from latent TB infection by quantifying spot-forming units (sfu). The investigation was a prospective study of contacts exposed to a case of contagious TB and cases of HIV-negative culture-proven TB referred over a 16-month period. Tuberculin skin tests (TSTs) and T-SPOT.TB were performed in 310 contacts 8–12u2005weeks after exposure. In subjects with culture-proven TB, T-SPOT.TB was performed within 2u2005weeks of initiation of treatment. The analysis included all contacts with a positive T-SPOT.TB result and all subjects with TB. TB contacts (nu200a=u200a127) and cases (nu200a=u200a58) were included. Mean±sd T-SPOT.TB results were 107±56 (range 1–207)u2005sfu for TB, 54±60 (7–239)u2005sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of >5u2005mm, and 19±27 (7–143)u2005sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of ≤5u2005mm. By receiver operating characteristic curve analysis, a threshold value of 49.5u2005sfu showed a sensitivity of 83% and specificity of 74% for distinguishing latent TB infection from TB. Although T-SPOT.TB results were significantly related to disease activity, the test cannot be recommended for the diagnosis of tuberculosis.

High hepatotoxicity of pyrazinamide and ethambutol for treatment of latent tuberculosis

Pyrazinamide (PZA) combined with either ethambutol (EMB) or a fluoroquinolone for 6–12 months is one of the treatments recommended for latent tuberculosis infection (LTBI) in contacts exposed to multidrug-resistant tuberculosis (MDR-TB). The aim of the present study was to describe the side effects related to combined PZA and EMB treatment given for LTBI, in contacts previously exposed to MDR-TB. In total, 12 consecutive contacts, all of African origin and aged 38±5u2005yrs, were treated with daily PZA (23±4u2005mg·kg−1) and EMB (17±4u2005mg·kg−1) at Geneva University Hospital outpatient clinic (Switzerland), as a result of contact-tracing procedures for two patients with contagious MDR-TB. Clinical status and liver function tests (aspartate aminotransferase (ALAT) and alanine aminotransferase (ASAT)) were monitored monthly. In seven cases (58%) treatment was discontinued after a median of 119 days, due to hepatic toxicity in six cases (ALAT or ASAT elevation more than four times the upper normal limit), and gastrointestinal symptoms in one case. In conclusion, combined pyrazinamide and ethambutol for latent tuberculosis infection may be associated with a high risk of hepatic toxicity, and warrants close monitoring. There is clearly a need for alternative preventive treatments for contacts exposed to multidrug-resistant tuberculosis.

Personality, anxiety and mood traits in patients with sleep-related breathing disorders: effect of reduced daytime alertness

OBJECTIVEnThe etiology of depression and personality disorders in patients with sleep-disordered breathing (SDB) is not well defined and it is still unclear if they are directly related to the severity of the disease. In this study we test the hypothesis as to whether daytime sleepiness largely contributes to appearance of mood disorders.nnnMETHODSnSixty patients diagnosed as having snoring (n=16) or OSA (n=44) were examined. Daytime sleepiness was assessed by the administration of the Epworth Sleepiness Scale (ESS) and by the Maintenance Wakefulness Test (MWT). The Hospital Anxiety (HAD-A) and Depression (HAD-D) Scale and the Temperament and Character Inventory (TCI) questionnaires were used for psychopathological evaluation.nnnRESULTSnThe mean HAD-A score was 6.9+/-0.45 and the average HAD-D score was 4.6+/-0.48, with no significant difference between snorers and OSA patients. Anxiety was present in 16% of cases and depression in 7%. The HAD-D score was related to the ESS score (R=0.37, P=0.003), the mean sleep latency at the MWT (R=-0.34, P=0.04), and the mean low SaO(2), ESS score alone explaining the 17% of variance in the HAD-D score. Compared to controls, there were no differences in almost all TCI scores, with novelty-seeking temperament score higher in patients. No relationships were found between HAD or TCI scores and apnea density.nnnCONCLUSIONSnWe conclude that among patients evaluated for SDB, higher depression scores show an association with reduced daytime alertness, which therefore may have important effects on mood.

Determinants of altered quality of life in patients with sleep-related breathing disorders

Recent reports have suggested that altered quality of life and well-being are reported by patients with sleep-related breathing disorders (SRBD). There seems to be no data available in the literature on factors underlying these behavioural consequences. In this study, health-related quality of life (HRQL) scores were examined in SRBD patients in order to establish which factors are implicated in these disturbances. The study group consisted of 130 patients: 49 snorers and 81 patients with obstructive sleep apnoea. The Medical Outcome Survey Short Form-36 questionnaire was administered the morning after the sleep study and scores for the eight dimension scores were obtained. Patients data were compared to normative sex- and age-matched data. In comparison with normal values, scores for all HRQL dimensions were decreased in SRBD patients, with a greater impact on subscores for “vitality”, “physical role”, “social functioning”, “mental health” and “role emotional” dimensions. While impairment in physical function was mostly influenced by sleep stage and obesity, subjective daytime sleepiness mainly affected the other dimensions. The authors conclude that the altered health-related quality of life of sleep-related breathing disorder patients is a multifactorial phenomenon depending on the interaction of sleep stages, daytime sleepiness and obesity, with no significant contribution of sleep fragmentation, hypoxaemia and apnoea recurrence.

Effect of patient education on self-management skills and health status in patients with asthma: a randomized trial.

We conducted a randomized clinical trial to assess the effectiveness of a newly established education program for adults with asthma. The program was designed to improve patients health and functional status. Hospitalized patients with asthma were randomly assigned to immediate education or a 6-month waiting list. The education program consisted of three group sessions, delivered by trained educators, and focused on improving patients self-management skills. Of 253 eligible patients, 131 agreed to participate (66 assigned to immediate education, 65 controls) and 115 (88%) completed the follow-up assessment at 6 months. At follow-up, most indicators of self-management skills and health and functional status had improved significantly among educated patients, but similar improvements were also seen among controls. The trial arms differed significantly on only four variables: patients in the immediate-education group were more likely to develop confidence in their asthma treatment (odds ratio adjusted for baseline [OR] = 2.9; 95% confidence interval [CI]: 1.0 to 8.1), to improve their knowledge of correct inhalation technique (OR = 2.4; 95% CI: 1.0 to 5.7), and to improve knowledge of the peak flow reading that warrants calling a physician (OR = 3.1; 95% CI: 1.4 to 6.7), but they improved less on the Asthma Quality of Life Questionnaire activity score (difference: -0.4 on a 1 to 7 scale; 95% CI: -0.8 to 0.0). Use of health services during follow-up was similar in the two groups. The education program did not enhance patients health and functional status, despite improving a few self-management skills. These results underscore the need for controlled evaluations of education programs.

Genome-wide association study of body mass index in 23 000 individuals with and without asthma

Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co‐morbidity between these conditions.

Upper and Lower Respiratory Tract Viral Infections and Acute Graft Rejection in Lung Transplant Recipients

Abstract Background. Lung transplant recipients are frequently exposed to respiratory viruses and are particularly at risk for severe complications. The aim of this study was to assess the association among the presence of a respiratory virus detected by molecular assays in bronchoalveolar lavage (BAL) fluid, respiratory symptoms, and acute rejection in adult lung transplant recipients. Methods. Upper (nasopharyngeal swab) and lower (BAL) respiratory tract specimens from 77 lung transplant recipients enrolled in a cohort study and undergoing bronchoscopy with BAL and transbronchial biopsies were screened using 17 different polymerase chain reaction—based assays. Results. BAL fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analyzed. We also compared paired nasopharyngeal and BAL fluid specimens collected in a subgroup of 283 cases. The overall viral positivity rate was 29.3% in the upper respiratory tract specimens and 17.2% in the BAL samples (P < .001). We observed a significant association between the presence of respiratory symptoms and positive viral detection in the lower respiratory tract (P = .012). Conversely, acute rejection was not associated with the presence of viral infection (odds ratio, 0.41; 95% confidence interval, 0.20–0.88). The recovery of lung function was significantly slower when acute rejection and viral infection were both present. Conclusions. A temporal relationship exists between acute respiratory symptoms and positive viral nucleic acid detection in BAL fluid from lung transplant recipients. We provide evidence suggesting that respiratory viruses are not associated with acute graft rejection during the acute phase of infection.

Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study

Background The incidence and outcomes of respiratory viral infections in lung transplant recipients (LTR) are not well defined. The objective of this prospective study conducted from June 2008 to March 2011 was to characterise the incidence and outcomes of viral respiratory infections in LTR. Methods Patients were seen in three contexts: study-specific screenings covering all seasons; routine post-transplantation follow-up; and emergency visits. Nasopharyngeal specimens were collected systematically and bronchoalveolar lavage (BAL) was performed when clinically indicated. All specimens underwent testing with a wide panel of molecular assays targeting respiratory viruses. Results One hundred and twelve LTR had 903 encounters: 570 (63%) were screening visits, 124 (14%) were routine post-transplantation follow-up and 209 (23%) were emergency visits. Respiratory viruses were identified in 174 encounters, 34 of these via BAL. The incidence of infection was 0.83 per patient-year (95% CI 0.45 to 1.52). The viral infection rates upon screening, routine and emergency visits were 14%, 15% and 34%, respectively (p<0.001). Picornavirus was identified most frequently in nasopharyngeal (85/140; 60.7%) and BAL specimens (20/34; 59%). Asymptomatic viral carriage, mainly of picornaviruses, was found at 10% of screening visits. Infections were associated with transient lung function loss and high calcineurin inhibitor blood levels. The hospitalisation rate was 50% (95% CI 30% to 70.9%) for influenza and parainfluenza and 16.9% (95% CI 11.2% to 23.9%) for other viruses. Acute rejection was not associated with viral infection (OR 0.4, 95% CI 0.1 to 1.3). Conclusions There is a high incidence of viral infection in LTR; asymptomatic carriage is rare. Viral infections contribute significantly to this populations respiratory symptomatology. No temporal association was observed between infection and acute rejection.

Do results of the T-SPOT.TB interferon-γ release assay change after treatment of tuberculosis?

BACKGROUNDnInterferon-gamma (IFN-gamma) production by lymphocytes exposed to antigens specific of Mycobacterium tuberculosis has been shown to correlate with antigen load and disease activity.nnnAIM OF STUDYnTo determine whether treatment of tuberculosis (TB) led to a decrease and/or a reversion of results of a IFN-gamma release assay (T-SPOT.TB, Oxford Immunotec, UK) and thus if T-SPOT.TB could be used to monitor response to treatment.nnnMETHODSnQualitative and quantitative analysis (SFUs: spot-forming units) of T-SPOT.TB in HIV-negative patients with TB, during initial 2 weeks of treatment (T0), at end of treatment (TE) and 6 months later (TE+6).nnnRESULTSnMean SFU (SD) was 75 (58; n=62) at T0, 46 (55; n=55) at TE, and 33 (46; n=41) at TE+6; positive rate was 98%, 93% and 98%, respectively. SFUs (paired samples, n=36) decreased significantly between T0 and TE; 2 reversions occurred between T0 and TE (6%), but none between TE and TE+6. Of 6 patients (17%) with an increase in SFUs between T0 and TE, 5 had a favourable outcome at TE and TE+6.nnnCONCLUSIONnDecrease in SFUs under treatment suggests a relationship with antigen load; however, persisting high SFUs were not predictive of unfavourable outcome and test reversion was rare.