Jean-Paul Janssens

Pneumonia in the very old

Pneumonia is a major medical problem in the very old. The increased frequency and severity of pneumonia in the elderly is largely explained by the ageing of organ systems (in particular the respiratory tract, immune system, and digestive tract) and the presence of comorbidities due to age-associated diseases. The most striking characteristic of pneumonia in the very old is its clinical presentation: falls and confusion are frequently encountered, while classic symptoms of pneumonia are often absent. Community-acquired pneumonia (CAP) and nursing-home acquired pneumonia (NHAP) have to be distinguished. Although there are no fundamental differences in pathophysiology and microbiology of the two entities, NHAP tends to be much more severe, because milder cases are not referred to the hospital, and residents of nursing homes often suffer from dementia, multiple comorbidities, and decreased functional status. The immune response decays with age, yet pneumococcal and influenza vaccines have their place for the prevention of pneumonia in the very old. Pneumonia in older individuals without terminal disease has to be distinguished from end-of-life pneumonia. In the latter setting, the attributable mortality of pneumonia is low and antibiotics have little effect on life expectancy and should be used only if they provide the best means to alleviate suffering. In this review, we focus on recent publications relative to CAP and NHAP in the very old, and discuss predisposing factors, microorganisms, diagnostic procedures, specific aspects of treatment, prevention, and ethical issues concerning end-of-life pneumonia.

Nocturnal monitoring of home non-invasive ventilation: the contribution of simple tools such as pulse oximetry, capnography, built-in ventilator software and autonomic markers of sleep fragmentation

Complex respiratory events, which may have a detrimental effect on both quality of sleep and control of nocturnal hypoventilation, occur during sleep in patients treated with non-invasive ventilation (NIV). Among these events are patient-ventilator asynchrony, increases in upper airway resistance (with or without increased respiratory drive) and leaks. Detection of these events is important in order to select the most appropriate ventilator settings and interface. Simple tools can provide important information when monitoring NIV. Pulse oximetry is important to ensure that adequate oxygen saturation is provided and to detect either prolonged or short and recurrent desaturations. However, the specificity of pulse oximetry tracings during NIV is low. Transcutaneous capnography helps discriminate between hypoxaemia related to ventilation/perfusion mismatch and hypoventilation, documents correction of nocturnal hypoventilation and may detect ventilator-induced hyperventilation, a possible cause for central apnoea/hypopnoea and glottic closure. Data provided by ventilator software help the clinician by estimating ventilation, tidal volume, leaks and the rate of inspiratory or expiratory triggering by the patient, although further validation of these signals by independent studies is indicated. Finally, autonomic markers of sympathetic tone using signals such as pulse wave amplitude of the pulse oximetry signal can provide reliable information of sleep fragmentation.

Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon‐γ release assay vs. tuberculin skin test

Background  Antitumour necrosis factor (anti‐TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon‐γ release assays (IGRA) have been shown to be more sensitive and specific than TST.

Risk Assessment of Tuberculosis in Immunocompromised Patients. A TBNET Study

RATIONALE In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. METHODS Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. MEASUREMENTS AND MAIN RESULTS Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. CONCLUSIONS Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Proposal for a systematic analysis of polygraphy or polysomnography for identifying and scoring abnormal events occurring during non-invasive ventilation

Non-invasive ventilation (NIV) is recognised as an effective treatment for chronic hypercapnic respiratory failure. Monitoring NIV during sleep may be preferable to daytime assessment. This paper reports the findings of an international consensus group which systematically analysed nocturnal polygraphic or polysomnographic tracings recorded with either volume-cycled or pressure-cycled ventilators. A systematic description of nocturnal respiratory events which occur during NIV is proposed: leaks, obstruction at different levels of the upper airway (glottis and/or pharynx), with or without decrease of respiratory drive and asynchrony.

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 8–12 weeks after exposure. In subjects with culture-proven TB, T-SPOT.TB was performed within 2 weeks of initiation of treatment. The analysis included all contacts with a positive T-SPOT.TB result and all subjects with TB. TB contacts (n = 127) and cases (n = 58) were included. Mean±sd T-SPOT.TB results were 107±56 (range 1–207) sfu for TB, 54±60 (7–239) sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of >5 mm, and 19±27 (7–143) sfu for contacts with positive T-SPOT.TB results and a TST induration diameter of ≤5 mm. By receiver operating characteristic curve analysis, a threshold value of 49.5 sfu 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±5 yrs, were treated with daily PZA (23±4 mg·kg−1) and EMB (17±4 mg·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.

Community-Acquired Pneumonia in Older Patients

OBJECTIVE: To document the prevalence of Legionella sp., Mycoplasma Pneumoniae and Influenza A and B in older patients hospitalized for community‐acquired pneumonia (CAP) or nursing‐home acquired pneumonia (NHAP) and to determine risk factors associated with fatal outcome or prolonged hospital stay.

Multimodal nutritional rehabilitation improves clinical outcomes of malnourished patients with chronic respiratory failure: a randomised controlled trial

Background In chronic respiratory failure (CRF), body composition strongly predicts survival. Methods A prospective randomised controlled trial was undertaken in malnourished patients with CRF to evaluate the effects of 3 months of home rehabilitation on body functioning and composition. 122 patients with CRF on long-term oxygen therapy and/or non-invasive ventilation (mean (SD) age 66 (10) years, 91 men) were included from eight respiratory units; 62 were assigned to home health education (controls) and 60 to multimodal nutritional rehabilitation combining health education, oral nutritional supplements, exercise and oral testosterone for 90 days. The primary endpoint was exercise tolerance assessed by the 6-min walking test (6MWT). Secondary endpoints were body composition, quality of life after 3 months and 15-month survival. Results Mean (SD) baseline arterial oxygen tension was 7.7 (1.2) kPa, forced expiratory volume in 1 s 31 (13)% predicted, body mass index (BMI) 21.5 (3.9) kg/m2 and fat-free mass index (FFMI) 15.5 (2.4) kg/m2. The intervention had no significant effect on 6MWT. Improvements (treatment effect) were seen in BMI (+0.56 kg/m2, 95% CI 0.18 to 0.95, p=0.004), FFMI (+0.60 kg/m2, 95% CI 0.15 to 1.05, p=0.01), haemoglobin (+9.1 g/l, 95% CI 2.5 to 15.7, p=0.008), peak workload (+7.2 W, 95% CI 3.7 to 10.6, p<0.001), quadriceps isometric force (+28.3 N, 95% CI 7.2 to 49.3, p=0.009), endurance time (+5.9 min, 95% CI 3.1 to 8.8, p<0.001) and, in women, Chronic Respiratory Questionnaire (+16.5 units, 95% CI 5.3 to 27.7, p=0.006). In a multivariate Cox analysis, only rehabilitation in a per-protocol analysis predicted survival (HR 0.27, 95% CI 0.07 to 0.95, p=0.042). Conclusions Multimodal nutritional rehabilitation aimed at improving body composition increased exercise tolerance, quality of life in women and survival in compliant patients, supporting its incorporation in the treatment of malnourished patients with CRF. Clinical Trial number NCT00230984.

Effect of a comprehensive, multidisciplinary, educational program on the use of antibiotics in a geriatric university hospital

Objectives: To assess the effect of a comprehensive, educational antibiotic management program designed to improve antibiotic use and reduce treatment costs in elderly patients with suspected urinary or respiratory tract infection.