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.

An evaluation of a new single-use flexible bronchoscope with a large suction channel: reliability of bronchoalveolar lavage in ventilated piglets and initial clinical experience.

A single-use flexible bronchoscope with a large suction channel has become available recently and we have evaluated this innovative device. Firstly, bronchoalveolar lavage was performed and quantified in ventilated piglets. Next, the bronchoscope was evaluated in three intensive care units and a satisfaction questionnaire was carried out. Sixteen bronchoalveolar lavages were performed in piglets with a recovery rate of 83 (79-86 [72-89])% of the instilled volume. Quality and performance of all devices tested was identical. The medical satisfaction questionnaire was as follows: 'acceptable' to 'very good' for quality of aspiration, manoeuvrability and quality of vision; 'very good' to 'perfect' for setting up and insertion. This encouraging preliminary evaluation demonstrates the effectiveness of this new single-use device, which may obviate the need for disinfection procedures and, thereby, eradicate a potential vector of patient cross-contamination.

[Guidelines for the management of chronic cough in adults]. / Recommandations de prise en charge de la toux chronique de l'adulte.

Patients with chronic cough experience major alteration in their quality of life. Given its numerous etiologies and treatments, this disease is a complex entity. To help clinicians involved in patient management of patients, guidelines have been issued by a group of French experts. They address definitions of chronic cough and initial management of patients with this pathology. We present herein the second-line tests that might be considered in patients whose coughing has persisted, notwithstanding initial management. The experts have also put forward a definition of unexplained or refractory chronic cough (URCC), the objective being to more precisely identify those patients whose cough persists despite optimal management. Lastly, these guidelines indicate the pharmacological and non-pharmacological interventions of use in URCC. Amitriptyline, pregabalin, gabapentin or morphine combined with speech and/or physical therapy are mainstays in treatment strategies. Other treatment options, such as P2X3 antagonists, are being developed and have generated high hopes among physicians and patients alike.

[Markers of severity and predictors of response to treatment in severe asthma]. / Marqueurs de sévérité et marqueurs prédictifs de réponse au traitement dans l'asthme sévère.

Asthma is a multifactorial disease with complex pathophysiology. Knowledge of its immunopathology and inflammatory mechanisms is progressing and has led to the development over recent years of increasingly targeted therapeutic strategies. The objective of this review is to pinpoint the different predictive markers of asthma severity and therapeutic response. Obesity, nasal polyposis, gastroesophageal reflux disease and intolerance to aspirin have all been considered as clinical markers associated with asthma severity, as have functional markers such as bronchial obstruction, low FEV1, small daily variations in FEV1, and high FeNO. While sinonasal polyposis and allergic comorbidities are associated with better response to omalizumab, nasal polyposis or long-term systemic steroid use are associated with better response to antibodies targeting the IL5 pathway. Elevated total IgE concentrations and eosinophil counts are classic biological markers regularly found in severe asthma. Blood eosinophils are predictive biomarkers of response to anti-IgE, anti-IL5, anti-IL5R and anti-IL4R biotherapies. Dupilumab is particularly effective in a subgroup of patients with marked type 2 inflammation (long-term systemic corticosteroid therapy, eosinophilia≥150/µl or FENO>20 ppb). Chest imaging may help to identify severe patients by seeking out bronchial wall thickening and bronchial dilation. Study of the patient's environment is crucial insofar as exposure to tobacco, dust mites and molds, as well as outdoor and indoor air pollutants (cleaning products), can trigger asthma exacerbation. Wider and more systematic use of markers of severity or response to treatment could foster increasingly targeted and tailored approaches to severe asthma.

[Diet and asthma: Better eating for better breathing?] / Alimentation et asthme : mieux se nourrir fait-il mieux respirer ?

Inhaled therapies are the cornerstone of asthma treatment. However, according to national and international guidelines, non-pharmacological interventions should not be neglected in asthma. It has been demonstrated that a healthy diet is beneficial to general health. Recently, the effect of diet on asthma has been highlighted in many studies. Two diets have been particularly studied: the Mediterranean diet (high in fruits and vegetables and low in fat) and the Western diet (high in saturated fat and low in fruits and vegetables). A beneficial effect of the Mediterranean diet and deleterious effect of the Western diet on the development or control of asthma has been shown in some studies even after adjustment for overweight. Study findings have not been unanimous, probably related to the complexity of conducting studies on a diet that may change from day to day for any individual subject. In addition, the effect of physical exercise, which is known to be beneficial in asthma, is rarely taken into account in these studies. However, studies on diet are becoming more complex with the use of specific dietary indices, which should bring interesting data in the future.

[Bronchial thermoplasty for severe asthma]. / Place de thermoplastie bronchique dans la prise en charge de l'asthme sévère.

Bronchial thermoplasty has been developed over the past fifteen years and is the first endoscopic technique approved in the management of severe asthma. This procedure uses radiofrequency applied to the airway wall to target bronchial smooth muscle. Patients treated in randomized controlled trials have experienced significant decreases in the use of rescue medications, urgent care visits, and exacerbations rate. The lack of reliable predictive markers of response to this expensive, minimally-invasive technique currently makes it a last-line treatment option. We review the principles and supposed mechanisms of action of this treatment, the results from the main trials and clinical registry data and discuss the place of bronchial thermoplasty in the current management of severe asthma. We also discuss perspectives to better characterize the mechanisms of action and identify the responder phenotype, the main challenge of current studies.

[Asthma and obesity in adults]. / Asthme et obésité de l'adulte.

Asthma is a chronic inflammatory airway disorder characterized by a multitude of phenotypes. Epidemiological studies show an increase in asthma prevalence in obese patients regardless of age. The association of asthma and obesity is now considered as a phenotype with its own clinical, biological and functional characteristics. Regarding the pathophysiology of asthma and obesity, numerous factors such as nutrition, genetic predisposition, microbiome, ventilatory mechanics and the role of adipose tissue have been identified to explain the heterogeneous characteristics of patients with asthma and obesity. In adult patients with asthma and obesity, respiratory symptoms are particularly prominent and atopy and eosinophilic inflammation is uncommon compared to normal weight asthma patients. Obese asthma patients experience more hospitalizations and use more rescue medications than normal weight asthmatics. Management of asthma in obese patients is complex because these patients have less response to the usual anti-asthmatic treatments. Weight loss through caloric restriction combined with exercise is the main intervention to obtain improvement of asthma outcomes. Bariatric surgery is an invasive procedure with interesting results.

Exhaled nitric oxide in chronic cough: A good tool in a multi-step approach.

INTRODUCTION: The impact of fractional exhaled nitric oxide (FENO) on the management of chronic cough (CC) is still inconclusive. The aim of the present study was to assess whether FENO is a good tool to predict the response to inhaled corticosteroids (ICS) in patients with CC. METHODS: Patients, referred for investigation of CC, had a FENO measurement determined as part of their first-line assessment. A methacholine test was performed as part of a second-line assessement. Patients were assigned to two groups according to their FENO values: a high FENO level group (â°¥25 ppb) and a normal FENO level group (<25 ppb). RESULTS: One hundred patients were included in the study. High FENO levels were found in 25 patients (25%). The proportion of patients who responded to ICS was significantly greater in the high FENO group compared to the normal FENO level group (86.4% vs 46.3%, P<0.05). FENO is a good tool to predict ICS response in patients with high FENO levels but a response to ICS cannot be ruled out in patients with normal FENO levels. In patients with normal FENO values, a methacholine test could be an interesting tool for a second-line assessment. Among the 13 patients with a positive methacholine test result, 11 responded to ICS whilst 2 did not. Of the patients with a negative methacholine test result, 3 responded to ICS whilst 13 did not. CONCLUSION: FENO may be a more reliable predictor of ICS response when used as part of a multi-step assessment procedure.

[Alveolo-interstitial pneumonia due to Temozolamide]. / Pneumonie alvéolo-interstitielle au témozolomide.

INTRODUCTION: Temozolomide is an alkylating agent approved for treatment of glioblastoma in association with radiotherapy. CASE REPORT: We report the case of a 56 year old woman presenting with alveolo-interstitial pneumonia after treatment with Temozolomide. Initially she received induction treatment with Temozolomide and concomitant radiotherapy for bifocal high grade glioblastoma. A month later she received, as scheduled, the first course of Temozolomide maintenance chemotherapy. Grade II dyspnoea developed a few days later. High resolution computed tomography showed alveolo-interstitial opacities with basal predominance, associated with alveolar nodules. Broncho-alveolar lavage showed a lymphocytosis. No bacteria were isolated from microbiological samples. A final diagnosis of drug-induced pneumonia was based on the time sequence and absence of other causes. CONCLUSION: There is little literature concerning the pulmonary toxicity of Temozolomide. However, our case report of drug-induced pneumonia and similar observations in the databases of regional pharmacovigilance centres suggest that this side effect should be included in the summary of product characteristics.

[Characteristics of non-pharmacological interventions in the elderly with COPD. Smoking cessation, pulmonary rehabilitation, nutritional management and patient education]. / Particularités de la prise en charge non médicamenteuse de la BPCO chez les sujets âgés. Réhabilitation, sevrage tabagique, nutrition et éducation thérapeutique.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder responsible for a high mortality and disability. People older than 65 years are more commonly affected than younger people and tend to present with more symptoms and a greater level of disability. Non-pharmacological interventions play an important role in the management of all patients with COPD and this is particularly true in the elderly. Given the improvement in quality of life and risk of hospitalization, smoking cessation should be promoted to patients of all ages. Increased physical activity is associated with reduced respiratory symptoms. Tests such as the "Short Physical Performance Battery" can be useful in frailer older people with COPD, while walking tests such as the 6-minute walk test are used as an assessment before pulmonary rehabilitation. Increased physical activity should be combined with nutritional management. Screening for undernutrition by questionnaire, body mass index and albumin quantification is recommended in the elderly. In case of undernutrition, oral supplementation seems to reduce the risk of re-admission. All these measures must be included in an education program adapted to the elderly comorbidities (hearing loss, isolation…).

Therapeutic antibodies: A new era in the treatment of respiratory diseases?

Respiratory diseases affect millions of people worldwide, and account for significant levels of disability and mortality. The treatment of lung cancer and asthma with therapeutic antibodies (Abs) is a breakthrough that opens up new paradigms for the management of respiratory diseases. Antibodies are becoming increasingly important in respiratory medicine; dozens of Abs have received marketing approval, and many more are currently in clinical development. Most of these Abs target asthma, lung cancer and respiratory infections, while very few target chronic obstructive pulmonary disease - one of the most common non-communicable causes of death - and idiopathic pulmonary fibrosis. Here, we review Abs approved for or in clinical development for the treatment of respiratory diseases. We notably highlight their molecular mechanisms, strengths, and likely future trends.

[Blomia tropicalis: A house dust mite in the tropics]. / Blomia tropicalis : un acarien sous les tropiques.

INTRODUCTION: Blomia tropicalis is a mite that belongs to the superfamily of Glycyphagidae. Initially described as a storage mite, it is now considered as a house dust mite of tropical and sub-tropical areas. STATE OF THE ART: Sensitization to this mite is very common in South America and Southeast Asia. Epidemiological studies have also found sensitization to this mite in Africa and Central America. Blo t 5 is the major allergen of B. tropicalis. Co-sensitization to other house dust mites such as Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) is very common. Cross-reactivity has been described but recombinant allergens revealed by molecular biology techniques do not explain this cross-reactivity. Sensitization to B. tropicalis seems to begin at the age of 36 months, the incidence increases until adulthood, and decreases from the age of 50. The involvement of B. tropicalis in allergic rhinitis and asthma is well described. It is also implicated in other allergic diseases. Few studies have assessed the therapeutic strategies available against this mite but immunotherapy is widely used. PERSPECTIVES: Studies are needed to better understand the role of B. tropicalis in human diseases and to develop specific treatments.

[Seasonality in asthma: Impact and treatments]. / La saisonnalité dans l'asthme : causes et approches thérapeutiques.

The role of seasons should be taken into account in the management of asthma. The environment varies between seasons and it is well documented that asthma is modulated by environment. Viruses cause asthma exacerbations peak, in winter, in adults while the peak is present in September in children. Allergens are probably a less powerful source of asthma exacerbation than viruses but pollen involvement in spring and summer and dust mites in autumn are indisputable. Air pollutants, present in summer during the hottest periods, are also highly involved in asthma exacerbations. Indoor air pollution, in winter, is also implicated in asthma disease. All these environmental factors are synergistic and increase the risk of asthma exacerbation. Therapies should be adapted to each season depending on environmental factors potentially involved in the asthma disease.

What are the characteristics of asthma patients with elevated serum IgG4 levels?

INTRODUCTION: IgG4 has recently been a subject of great interest in human pathology. No data are available about the characteristics of asthma patients with elevated IgG4 levels. POPULATION AND METHODS: An observational study was conducted from January 2006 to March 2015 in a difficult-to-treat population of asthma patients. Twenty-six difficult-to-treat asthma patients with elevated serum IgG4 levels (IgG4/IgG ratio up to 10%) were compared with a control population of 98 difficult-to-treat asthma patients with normal serum IgG4. Blood eosinophilia, total IgE and FeNO were compared between groups to better characterize asthma patients with elevated serum IgG4 levels. RESULTS: Median IgG4 concentrations were 1.72 g/l [1.19-2.36] and 0.22 g/l [0.10-0.49] in the elevated IgG4 group and normal Ig4 group, respectively. Median blood eosinophilia was more than three times higher in patients with elevated serum IgG4 levels than in controls (0.75 10(9)/L [IQR 0.54-1.78] vs 0.22 10(9)/L [IQR 0.09-0.54] respectively, p < 0.0001). Total IgE was twice as high (264.5 kUI/l [IQR 166.3-779] vs 126 kUI/l [IQR 26-350] respectively; p < 0.05) and FeNO was nearly twice as high (61 [IQR 41-111] ppb vs 35 [IQR 23-51] ppb, p < 0.001). Allergic broncho-pulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (EGPA) were observed in the asthma patients with elevated serum IgG4. Ten patients had unexplained increased blood eosinophilia. CONCLUSION: Asthma patients with elevated IgG4 levels have significantly higher blood eosinophilia, total IgE and FeNO. ABPA and EGPA are observed in patients with elevated serum IgG4.