Lung function parameters in omalizumab responder patients: An interesting tool?

BACKGROUND: Omalizumab, an anti-IgE antibody, is used to treat patients with severe allergic asthma. The evolution of lung function parameters over time and the difference between omalizumab responder and nonresponder patients remain inconclusive. The objective of this real-life study was to compare the changes in forced expiratory volume in 1 second (FEV1) of omalizumab responders and nonresponders at 6 months. METHODS: A multicenter analysis was performed in 10 secondary and tertiary institutions. Lung function parameters (forced vital capacity (FVC), pre- and postbronchodilator FEV1, residual volume (RV), and total lung capacity (TLC) were determined at baseline and at 6 months. Omalizumab response was assessed at the 6-month visit. In the omalizumab responder patients, lung function parameters were also obtained at 12, 18, and 24 months. RESULTS: Mean prebronchodilator FEV1 showed improvement in responders at 6 months, while a decrease was observed in nonresponders (+0.2±0.4 L and -0.1±0.4 L, respectively, P<.01). After an improvement at 6 months, pre- and postbronchodilator FEV1 remained stable at 12, 18, and 24 months. The FEV1/FVC remained unchanged over time, but the proportion of patients with an FEV1/FVC ratio <0.7 decreased at 6, 12, 18, and 24 months (55.2%, 54.0%, 54.0%, and 44.8%, respectively, P<.05). Mean RV values decreased at 6 months but increased at 12 months and 24 months (P<.05). Residual volume/total lung capacity (RV/TLC) ratio decreased at 6 months and remained unchanged at 24 months. CONCLUSION: After omalizumab initiation, FEV1 improved at 6 months in responder patients and then remained stable for 2 years. RV and RV/TLC improved at 6 months.

Pulmonary arterial hypertension in adult onset Still's disease: a case report of a severe complication.

BACKGROUND: Adult onset of Still's disease (AOSD) is a rare systemic inflammatory disease. Cardiorespiratory complications are mainly represented by pleural and pericardial disorders and are less frequent than cutaneous and articular complaints. Pulmonary arterial hypertension (PAH) occurring in AOSD is rarely described in literature. CASE PRESENTATION: We present the case of a young patient who developed severe PAH 2 years after diagnosis of AOSD. This is a rare and severe complication which is probably underestimated. CONCLUSIONS: PAH in AOSD can be lethal, and unfortunately its occurrence is unpredictable. Echocardiographic screening of AOSD patients should be evaluated in further trials. Currently, the most suitable treatment is still unknown.

Adherence in severe asthma.

Adherence in asthma is an important cause for concern. Although nearly 50% of asthma patients are considered poorly adherent to therapeutic advices, adherence is still difficult to assess, understand and improve despite major medical consequences. In this review, we revisited the literature of the last 10 years related to adherence in severe asthma. The concepts have changed and "compliance" is usually replaced by "adherence". Assessment of adherence is addressing ethical issues, but provides important insight into difficult-to-treat asthma. Different tools have been used but none is routinely recommended. Health-related outcomes (poor control, exacerbations, hospitalizations, lung function decline), which are clearly associated with severe asthma, are often worsened by non-adherence with consequences also on patient related outcomes (quality of life). The potential behaviour associated with non-adherence and all other related factors including easy-to-recognize psychological traits can help for patient's future management. Therapeutic educational interventions have been recognized with a scientifically proven efficiency even though evolution and improvements are needed. A multidisciplinary approach is required in severe asthma. Therapeutic adherence for a given patient is always a prerequisite to any other aspects when addressing severe asthma phenotypes. Severe asthma should be considered only in those who still experienced poor asthma outcomes despite optimal adherence. At a glance, poor adherence and severe asthma should be considered antinomic. Better understanding of the causes and customised management are potential future directions.

Pulmonary manifestations of leptospirosis.

BACKGROUND: Pulmonary manifestations in leptospirosis are considered a major complication and are related to a poor prognosis. We present a large series of patients with pulmonary involvement using a practical approach based on the presence of acute respiratory failure (ARF). METHODS: A retrospective study of patients with confirmed leptospirosis. RESULTS: One hundred and sixty-nine patients with a laboratory-confirmed diagnosis of leptospirosis were investigated. One hundred and thirty-four patients (36.7±14 years of age) had pulmonary involvement. Severe pulmonary involvement was defined by evidence of ARF. Univariate analysis found the following factors related to severe pulmonary leptospirosis: dyspnoea (OR=10.14, p<0.0001), pulmonary crepitations (OR=4.8, p<0.0004), abnormal chest X-ray (OR=9.88, p<0.007) with alveolar shadowing (OR=8.12, p<0.0001), oliguria/anuria (OR=5.48, p<0.0001), hepatomegaly (OR=7.11, p< 0.0001), shock (OR=8.38, p< 0.0001), ICU admission (OR=60.08, p< 0.0001), dialysis (OR=4.87, p< 0.001), mechanical ventilation (OR=216, p< 0.0001) and development of nosocomial infection (OR=21.5, p< 0.0001). The mortality rate was significantly different between severe (40%) and non-severe (5.3%) pulmonary forms (OR=11.87, p< 0.0001). Multivariate analysis found two independent factors related to severe pulmonary involvement: dyspnoea (OR=10.18, p< 0.0001) and oliguria/anuria (OR=4.87, p< 0.0009). We performed a multivariate analysis to assess independent factors related to mortality and found: mechanical ventilation requirement (OR=27.85, p< 0.0001) and AST greater than 150 IU/L (OR=4.57, p< 0.02). Haemoptysis was associated with survival (OR=0.2, p< 0.02). CONCLUSIONS: Severe pulmonary involvement in leptospirosis is associated with extensive disease involving other organs. The association of multiple factors is associated with severe forms of the disease and a high mortality rate.

[Pulmonary manifestations of leptospirosis]. / Manifestations pulmonaires de la leptospirose.

BACKGROUND: Pulmonary manifestations in leptospirosis are considered a major complication, and are related to a poor prognosis. We present a large series of patients with pulmonary involvement using a practical approach based on the presence of acute respiratory failure (ARF). METHODS: A retrospective study of patients with confirmed leptospirosis. RESULTS: 169 patients with a laboratory-confirmed diagnosis of leptospirosis were investigated. 134 patients (36.7 + or - 14 years of age) had pulmonary involvement. Severe pulmonary involvement was defined by evidence of acute respiratory failure. Univariate analysis found the following factors related to severe pulmonary leptospirosis: dyspnoea (OR 10.14, p<0.0001), pulmonary crepitations (OR 4.8, p<0.0004), abnormal chest X Ray (OR 9.88, p<0.007) with alveolar shadowing (OR 8.12, p<0.0001), oliguria/anuria (OR 5.48, p<0.0001), hepatomegaly (OR 7.11, p<0.0001), shock (OR 8.38, p<0.0001), ICU admission (OR 60.08, p<0.0001), dialysis (OR 4.87, p<0.001), mechanical ventilation (OR 216, p<0.0001) and development of nosocomial infection (OR 21.5, p<0.0001). The mortality rate was significantly different between severe (40%) and non-severe (5.3%) pulmonary forms (OR 11.87, p<0.0001). Multivariate analysis found 2 independent factors related to severe pulmonary involvement: dyspnoea (OR 10.18, p<0.0001), and oliguria/anuria (OR 4.87, p<0.0009). We performed a multivariate analysis to assess independent factors related to mortality and found: Mechanical ventilation requirement (OR 27.85, p<0.0001) and ASAT>150 UI/L (OR 4.57, p<0.02). Haemoptysis was associated with survival (OR 0.2, p<0.02). CONCLUSION: Severe pulmonary involvement in leptospirosis is associated with extensive disease involving other organs. The association of multiples factors is associated with severe forms of the disease and a high mortality rate.

[Asthma on the island of Reunion: an analysis of the severity and therapeutic management]. / Asthme à l'île de la Réunion: analyse de la sévérité et de la prise en charge thérapeutique.

INTRODUCTION: Asthma is a common condition on the island of La Reunion but there are no epidemiological studies that analyse the prevalence, severity and management of the patients. METHODS: Two studies were undertaken: a CPAM (health insurance) study of 187 patients and an analysis of the data from 253 patients attending a specialist hospital clinic. RESULTS: In these two studies we found 40% of patients were in GINA group 3 compared with 10% in metropolitan France. Recourse to the emergency department and admission to intensive care were common. There was under-evaluation by the treating physicians who did not classify patients correctly. This under-evaluation also occurred in prescribing with only 1/3 of asthmatics in stages 2 and 3 receiving inhaled corticosteroids. Patient education was poor with 30% receiving a demonstration of inhaler technique and 31% a functional evaluation. CONCLUSION: These studies show that the severity profile of asthma on La Reunion is comparable to that in other oceanic countries like Australia and New Zealand rather than metropolitan France. A population study is needed to assess the prevalence of asthma on the island of La Reunion.

Nitrogen washout slope in poorly controlled asthma.

Short-term control of asthma is often lacking even though forced expiratory volume in 1 s (FEV1) remains above normal value. Small airways are a potential key site of persistent inflammation and structural modification. Noninvasive assessment of small airways was found to be difficult, but the computerized single breath nitrogen washout test (SBNT) has been recently successfully reintroduced with this aim. Twenty-four asthmatics (13 females) of various severity but with normal FEV1 were compared with 24 healthy volunteers (13 females) and studied at steady-state after bronchodilatation (400 microg salbutamol). Spirometric values, plethysmographic data, phase III (slope of phase III of the SBNT, dN2) and IV [closing volume (CV), with closing capacity (CC) = CV + residual volume (RV)] of the SBNT were checked. Asthma severity, recent control, exacerbation rate, and therapy requirements were assessed on the basis of validated questionnaires (ACQ) and international guidelines. Patients were prospectively pooled into two equal groups according to their exacerbation rate. The reproducibility of the measurements obtained on 2 following days was assessed. All plethysmographic values, except total lung capacity (TLC), differentiated asthmatic patients from controls. The CC/TLC [124 (117-148) vs 117 (112-123), P = 0.04] and dN2 [110 (99-190) vs 94 (75-111), P = 0.02] were increased in asthma. The dN2 was significantly increased in patients with frequent exacerbations [100 (83-105) vs 195 (141-212), P = 0.0005]. A correlation was obtained between dN2 and recent asthma control (rho: 0.62; P = 0.003), number of exacerbations (rho: 0.71, P = 0.0008), and RV/TLC (rho: 0.49, P = 0.026). This study demonstrated that ventilation inequalities assessed by dN2 represent an important indicator of poor asthma control and high exacerbation rate in high symptom perceivers. New therapies focused on small airways should now be developed.

Moxifloxacin monotherapy compared to amoxicillin-clavulanate plus roxithromycin for nonsevere community-acquired pneumonia in adults with risk factors.

The objective of this study was to assess the efficacy and safety of moxifloxacin versus amoxicillin-clavulanate plus roxithromycin (comparator) in adult community-acquired pneumonia (CAP) patients with risk factors. In this comparative, randomized, multicenter, open-label study, patients hospitalized for CAP received a 10-day oral treatment with either moxifloxacin (400 mg o.d.) or amoxicillin-clavulanate (1,000/125 mg t.i.d.) plus roxithromycin (150 mg b.i.d.). Clinical and bacteriological outcomes were assessed during test of cure and follow-up visits (5-7 days and 21-28 days after the end of treatment, respectively). Of 349 randomized patients, 346 were included in the intent-to-treat analysis and 289 in the per-protocol analysis. Their baseline characteristics were comparable. The most frequent risk factors for mortality were age >65 years (50.0%), alcoholism (23.1%), and comorbidities (50.6%); chronic obstructive pulmonary disease (COPD) (25.4%) and diabetes mellitus (13.6%) were the most common associated comorbidities. A causative pathogen was documented in 66 of 346 (19.1%) of the patients (including 21 with positive blood cultures). Respective per-protocol clinical success rates at test-of-cure (primary efficacy endpoint) for moxifloxacin and comparator were 131 of 151 (86.8%) and 120 of 138 (87.0%), with a 95% confidence interval (CI) of -8.0-7.6 for the difference. Bacteriological success rates (eradication) were 23 of 30 (76.7%) and 23 of 31 (74.2%); rates for patients with positive blood cultures were 10 of 14 and 4 of 6. Persistent clinical success rates at follow-up were 118 of 120 (98.3%) and 102 of 106 (96.2%), with a 95%CI of -2.2-6.4 for the difference. The intent-to-treat analysis confirmed these results. Adverse events associated with moxifloxacin and the comparator drug were reported for 42 of 171 (24.6%) and 50 of 175 (28.6%) of the patients, respectively, and comprised predominantly digestive disorders, which occurred in 9.4% and 21.1%. On the basis of these results, once-daily oral moxifloxacin alone is as effective as amoxicillin-clavulanate plus roxithromycin for the treatment of CAP in patients with risk factors.

Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD.

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airways.

Severe community-acquired pneumonia: assessment of microbial aetiology as mortality factor.

Community-acquired pneumonia (CAP) remains a major cause of mortality. The aetiology of CAP has rarely been identified as a mortality risk factor. A prospective study was conducted to assess the prognostic factors of CAP patients admitted to the intensive care unit (Centre Hospitalier Departmental Felix Guyon, St Denis de la Reunion, France), with a special emphasis on microbial aetiology. All variables assessing severity were collected, with a special emphasis on microbial investigations. Among 112 immunocompetent patients (mean+/-SD age 54.7+/-15.1 yrs), 84% were male. Severity of CAP was demonstrated by mortality rate (43%), shock (48%), simplified acute physiology score (SAPS; 46.4+/-21.6) and mechanical ventilation support (82%). Mean risk factor score was 2.2+/-1.2. Microbiological identification was obtained in 78.6% of cases, with positive blood culture in 33%. Most frequently, microbial agents were Streptococcus pneumoniae and Klebsiella pneumoniae (42% and 22%, respectively). The univariate analysis recorded the usual mortality variables: age, alcohol consumption, SAPS, shock, mechanical ventilation, positive end expiratory pressure level, positive blood culture, multilobar infiltrates on chest radiograph, neutropenia, and acidosis, and found K. pneumoniae (versus S. pneumoniae, and all CAP) as a mortality factor. The multivariate analysis demonstrated that septic shock (relative risk (RR) 141), K. pneumoniae CAP (RR 27), SAPS (RR 10.7) and positive blood culture (RR 2.7) were independent factors related to death. In conclusion, the present study found that the microbial aetiology, Klebsiella pneumoniae, was an independent risk factor for mortality in severe community-acquired pneumonia.

[Chylothorax: an unexpected complication of artificial ventilation in severe acute asthma]. / Une complication inattendue de l'asthme aigu grave sous ventilation artificielle: le chylothorax.

INTRODUCTION: Complications of mechanical ventilation for severe acute asthma are common and are related essentially to barotrauma. However, the incidence has declined in recent years thanks to different techniques of ventilation. CASE REPORT: We report a case of spontaneous chylothorax occurring during the course of ventilation in a patient with severe acute asthma where the ventilatory parameters were in accordance with current recommendations. Recovery was straightforward with resolution of the chylothorax and no recurrence either immediately or later. Exhaustive clinical, biological and morphological investigations failed to find any cause other than the mechanical ventilation. CONCLUSION: This case of chylothorax may be considered as a rare barotraumatic complication of severe acute asthma.

Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

[The value and limits of Palmaz's prosthesis in the treatment of tracheobronchial stenosis]. / Intérêts et limites de la prothèse de Palmaz dans le traitement des sténoses trachéobronchiques.

The use of endobronchial prosthesis may be indispensable to maintain patency of the airways. We report our experience using Palmaz's prosthesis in four patients. The results were satisfactory in one patient but we have been confronted with three failures and one grave complication. The failures were linked to unsuitable properties of this prosthesis which has led us limit its use whilst waiting for newer studies.

[Importation of Plasmodium falciparum malaria, in Réunion Island, from 1993 to 1996: epidemiology and clinical aspects of severe forms]. / Le paludisme d'importation à Plasmodium falciparum, à l'ile de La Réunion, de 1993 à 1996: épidémiologie et aspects cliniques des formes graves.

Located in the Indian ocean, Reunion island, a French overseas territory, is free of malaria since the 1960's. As malaria is still highly endemic in the neighbouring countries, imported cases are averaging 130 to 150 cases per year. From 1993 to 1996, about 483 cases of imported malaria were admitted in Reunion. Five severe complicated Plasmodium falciparum malaria cases occurring in non-immune persons, required further treatment in the intensive care unit (age 40 +/- 8 years, duration: 14.8 +/- 7.4, SAPS: 21 +/- 10). Three patients died. As short-stay travellers, patients were contaminated in Madagascar (4) and in Malawi (1) and presented with an associated pathology: alcohol and tobacco abuses (2 cases), AIDS (1 case). In all cases, chemoprophylaxis was either inadequate (chloroquine alone, 3 cases) or absent (2 cases) and the diagnosis and the appropriate treatment were delayed. Moreover, patients were either self-treating themselves, or initially refused to be admitted. Parasitemia was very high. Two patients died within an hour following their admission before diagnosis could be made and quinine treatment be initiated (rupture of the spleen, multiple organ failure). One patient died at day 7 (acute respiratory distress syndrome, renal failure). Two survived under respiratory assistance and hemodialysis and presented the usual intensive care complications (respiratory nosocomial infection, acute cholecystitis). In Réunion island, imported P. falciparum still accounts for a high rate of morbidity and few fatalities, despite a sophisticated curative health system. Delay in diagnosis and institution of an appropriate treatment is frequent in non-immune persons who develop fever and non-specific symptoms. It markedly increases the risk of complications and death from falciparum malaria as well as morbidity cofactors. Emphasis must be placed on appropriate information of health personnel and travellers.

[Neuromeningeal cryptococcosis and alcoholic cirrhosis]. / Cryptococcose neuro-méningée et cirrhose alcoolique.

Cryptococcal infections are usually described in immunosuppressed patients, but have also been described in patients with cirrhosis. We report a case of cryptococcal meningitis in a 62 year old man with Child class C alcoholic cirrhosis. Clinical signs associated mental confusion and discrete meningeal stiffness without fever. Diagnosis was confirmed by lumbar puncture which identified specific antigens and isolated Cryptococcus on Sabouraud medium. In patients with cirrhosis, cryptococcal meningitis infection should be considered in cases of isolated and unexplained mental confusion.