Thierry Chinet

Acute Respiratory Failure Involving an R Variant of Mycobacterium abscessus

ABSTRACT We report the case of a cystic fibrosis patient colonized with a smooth-morphotype form of Mycobacterium abscessus who developed acute respiratory failure with the emergence of an isogenic rough (R) variant while he was recovering from peritonitis-induced shock. This report emphasizes the role of R forms in severe M. abscessus infections.

Diagnosis and treatment of pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: An overview.

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomic dominant disorder, which is characterized by the development of multiple arteriovenous malformations in either the skin, mucous membranes, and/or visceral organs. Pulmonary arteriovenous malformations (PAVMs) may either rupture, and lead to life-threatening hemoptysis/hemothorax or be responsible for a right-to-left shunting leading to paradoxical embolism, causing stroke or cerebral abscess. PAVMs patients should systematically be screened as the spontaneous complication rate is high, by reaching almost 50%. Neurological complications rate is considerably higher in patients presenting with diffuse pulmonary involvement. PAVM diagnosis is mainly based upon transthoracic contrast echocardiography and CT scanner examination. The latter also allows the planification of treatments to adopt, which consists of percutaneous embolization, having replaced surgery in most of the cases. The anchor technique consists of percutaneous coil embolization of the afferent pulmonary arteries of the PAVM, by firstly placing a coil into a small afferent arterial branch closely upstream the PAVM. Enhanced contrast CT scanner is the key follow-up examination that depicts the PAVM enlargement, indicating the various mechanisms of PAVM reperfusion. When performed by experienced operators as the prime treatment, percutaneous embolization of PAVMs, is a safe, efficient and sustained therapy in the great majority of HHT patients.

Diffuse Pulmonary Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia: Long-term Results of Embolization According to the Extent of Lung Involvement

OBJECTIVES To review the safety of embolization in patients affected with hereditary hemorrhagic telangiectasia (HHT) presenting with diffuse pulmonary arteriovenous malformations (PAVMs). To correlate the initial presentation and long-term results of embolization according to the distribution of PAVMs. MATERIALS AND METHODS All consecutively treated patients were divided into three groups, according to the involvement of every subsegmental pulmonary artery (group 1), segmental artery (group 2), or both (group 3) of at least one lobe. Age, sex, initial clinical presentation, and Pao(2) were recorded before embolization. Per and postprocedural complications were carefully recorded. Clinical outcome and imaging follow-up were obtained at 6 months and annually thereafter. RESULTS Thirty-nine patients (31 women, 8 men; mean age, 35 years), all of them with bilateral lung involvement, were treated. Group 1 consisted of 8, group 2 of 17, and group 3 of 14 patients. Dyspnea was present in 35 of the patients (90%) and cyanosis in 17 patients (44%). Preembolization Pao(2) was different between groups 1 (52.6 +/- 11.6 mm Hg) and 3 (70.7 +/- 14.1 mm Hg). Neurologic events were more frequently reported before treatment in group 1 (62.5%) than in group 2 (35%) or in group 3 (43%). Eighty percent of patients reported improvement in their dyspnea after embolization. Pao(2) levels improved more in group 2 than in groups 1 and 3. Eight ischemic or infectious complications occurred in 4 patients (10%) due to reperfusion of embolized PAVMs or enlargement of non-embolized PAVMs. Complete and partial treatment success was reported using CT scanning in 59% and 38% of cases, respectively. CONCLUSION Dyspnea and paradoxical embolism are frequently encountered in HHT patients with diffuse PAVMs. Prevention of complications and improvement of dyspnea can be achieved after successful embolization in most patients. Better improvement of Pao(2) can be achieved in group 2.

Update on the roles of distal airways in COPD

This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

Serial computed tomography and lung function testing in pulmonary Langerhans’ cell histiocytosis

Little is known about longitudinal lung function variation in patients with pulmonary Langerhans’ cell histiocytosis (LCH). The contribution of serial lung computed tomography (CT) to managing these patients has not been evaluated. This long-term retrospective study included 49 patients who were serially evaluated by lung CT and pulmonary function tests. The lung function variation was categorised as improvement or deterioration. The extent of the CT lesions was correlated with lung function. Lung function deteriorated in ∼60% of the patients. Forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DL,CO) were the parameters that most frequently deteriorated. A subgroup of patients experienced a dramatic decline in FEV1 within 2 yrs of diagnosis. Airway obstruction was the major functional pattern observed. In a multivariate analysis, % predicted FEV1at diagnosis was the only factor associated with the incidence of airway obstruction. The increase in cystic lesions on the lung CTs was associated with impaired lung function but did not anticipate the decline in FEV1 or DL,CO. Serial lung function tests are essential for following patients with pulmonary LCH, who frequently develop airway obstruction. A lung CT at diagnosis is informative, but routine sequential CTs seem less useful. A prospective study is needed to characterise those patients with early progressive disease.

Small airways diseases, excluding asthma and COPD: an overview.

This review is the summary of a workshop on small airways disease, which took place in Porquerolles, France in November 2011. The purpose of this workshop was to review the evidence on small airways (bronchiolar) involvement under various pathophysiological circumstances, excluding asthma and chronic obstructive pulmonary disease. Histopathological patterns associated with small airways disease were reviewed, including cellular and obliterative bronchiolitis. Many pathophysiological conditions have been associated with small airways disease including airway infections, connective tissue diseases and inflammatory bowel diseases, bone marrow and lung transplantation, common variable immunodeficiency disorders, diffuse panbronchiolitis, and diseases related to environmental exposures to pollutants, allergens and drugs. Pathogenesis, clinical presentation, a computed tomography scan and pulmonary function test findings are reviewed, and therapeutic options are described with the objective of providing an integrative approach to these disorders.

Ion and liquid transport across the bronchiolar epithelium.

The proper homeostasis of the airway surface liquid (ASL) depends on transepithelial ion and fluid transport and is critically important for lung defence, and more specifically for mucociliary transport. In cystic fibrosis (CF), abnormal ion and fluid transport lead to depleted ASL volume resulting in mucus plugs and recurrent lung infections. Like bronchi, human bronchioles exhibit amiloride-sensitive Na(+) absorption and cyclic-AMP and Ca(2+)-activated Cl(-) secretion. However, cyclic-AMP-stimulated Cl(-) and fluid secretion appears to be quantitatively more important in bronchioles than in bronchi. In CF bronchioles, like in CF bronchi, the ASL height is reduced because of an abnormally persistent Na(+) absorption, combined with a lacking CFTR-dependent Cl(-) secretion. The precocity and severity of the bronchiolar disease in CF could be attributed in part to the more important role of CFTR-dependent Cl(-) secretion and fluid secretion, and the lack of compensatory ATP-driven Cl(-) secretion and fluid secretion, in bronchioles compared to bronchi.

Reperfusion of Complex Pulmonary Arteriovenous Malformations After Embolization: Report of Three Cases

The purpose of this report is to discuss the different mechanisms of reperfusion of pulmonary arteriovenous malformations (PAVMs) after embolization. Transcatheter embolotherapy is currently the first-line treatment of PAVMs to prevent neurologic complications or pulmonary hemorrhage. Initial good results can be expected but we report three cases of reperfusion of complex large PAVMs after coil embolization. After adequate embolization, reperfusion of PAVMs may occur by several mechanisms including recanalization of embolized arteries, recruitment of normal arterial branches, growth or enlargment and development of a systemic arterial supply.

Ambulatory Inhalation Therapy in Obstructive Lung Diseases

The inhalation route is widely used for the treatment of obstructive lung diseases, because administered drugs have a high therapeutic index as they reach their target directly; this requires that they be of adequate size to penetrate the conducting airways, i.e. 2-5 microns. Pressurized inhalers were the first reliable metered-dose devices available, and are still the most frequently used. However, metered-dose inhaler (MDI) suspensions will have to be reformulated: they contain chlorofluorocarbons (CFCs), whose production has to be stopped within a few years, as they affect the stratosphere. Another limitation of MDI usage is paradoxical bronchospasm; this phenomenon, however, occurs in a low number of patients and is rarely clinically relevant. The main cause of concern with MDIs is their misuse by more than 50% of patients, which leads to a reduced lung deposition and clinical efficacy. Therefore, other inhalation devices have been developed: spacers, dry-powder inhalers (DPIs), and breath-actuated MDIs have been shown to increase lung deposition of drugs in poor coordinators. However, all have limitations which may have varying consequences on clinical efficacy: cumbersome dimensions of spacers, effect of inspiratory flow rate and humidity on lung deposition of dry powders, need for reformulation with CFC-free gases for breath-actuated pressurized inhalers. Reformulation of MDI aerosols is a complex procedure, which may not be feasible for all drugs. The new products need extensive toxicological and clinical testing, as some of their characteristics may differ from those of their predecessors.

Prospective screening for ALK: clinical features and outcome according to ALK status.

The aim of this study was to analyse the clinico-pathological characteristics and outcomes of a cohort of French patients who were prospectively screened for Anaplastic Lymphoma Kinase (ALK) rearrangement. One hundred and sixteen consecutive patients screened for ALK rearrangement to be recruited into a crizotinib registration trial were included from eight French centres. ALK rearrangement was detected by fluorescence in situ hybridization. Seventeen patients (14.6%) were positive for ALK. ALK+ patients were younger (p = 0.049) and more likely to be males (p=0.032), non- or light-smokers (p = 0.048) and without underlying respiratory disease (p=0.025) compared to ALK- patients. Thyroid-transcription factor-1 expression was present in all ALK+ tumours. ALK+ tumours tended to have lymph node and brain metastases. In multivariate analyses, gender, smoking history and N stage were independently associated with ALK status. Median overall survival (OS) was not reached for ALK+ patients and was significantly longer than for ALK- patients (hazard ratio for death for ALK- patients 2.98; 95% CI [1.29-6.90], p=0.01). French ALK+ patients present a specific phenotype. ALK rearrangement should be determined to improve OS with an effective targeted therapy.