Goblet cell hyperplasia as a feature of neutrophilic asthma.

BACKGROUND: Goblet cell hyperplasia (GCH) is a pathological finding classically reported across asthma severity levels and usually associated with smoking. Multiple biological mechanisms may contribute to excessive mucus production. OBJECTIVE: We aimed to decipher the clinical meanings and biological pathways related to GCH in non-smokers with asthma. METHODS: Cough and sputum assessment questionnaire (CASA-Q) responses at entry and 1 year later were compared to clinical and functional outcomes in 59 asthmatic patients. GCH was assessed through periodic-acid shift (PAS) staining on endobronchial biopsies obtained at entry in a subset of 32 patients. RESULTS: Periodic-acid shift-staining analysis revealed a double wave distribution discriminating patients with (>10% of the epithelial area) or without GCH. CASA-Q scores were mostly driven by overall asthma severity (P < 0.0001). CASA-Q scores remained stable at 1 year and were independently associated with BAL eosinophil content irrespective of the presence of GCH. GCH was unrelated to the presence of bronchiectasis at CT, GERD or chronic rhinosinusitis, but correlated well with neutrophilic inflammatory patterns observed upon BAL cellular analysis (P = 0.002 at multivariate analysis). BALF bacterial loads were unrelated to GCH or to CASA-Q. CONCLUSIONS AND CLINICAL RELEVANCE: Goblet cell hyperplasia is disconnected from chronic cough and sputum when assessed by a specific questionnaire. GCH is related to neutrophilic asthma whereas symptoms are related to airway eosinophilia. The clinical counterpart of GCH is unlikely assessed by the CASA-Q.

Hereditary lysozyme amyloidosis with sicca syndrome, digestive, arterial, and tracheobronchial involvement: case-based review.

Lysozyme amyloidosis (ALys) is a rare autosomal dominant hereditary systemic amyloidosis associated with a large spectrum of clinical manifestations. ALys phenotype mainly involves the digestive tract, liver and spleen, kidneys, lymph nodes, skin, and lachrymal and salivary glands. Very recently, cardiac involvement and peripheral neuropathy associated with a new p.Leu102Ser variant of lysozyme have been documented. In the present observation, we extend the phenotypic heterogeneity of ALys to the tracheobronchial tree with histologically proven bronchial ALys-amyloid deposits. We report the case of a 62-year-old man of Italian origin (Piedmont) diagnosed with ALys associated with the p.Trp82Arg variant. The patient complained of upper digestive symptoms, sicca syndrome, and lately recurrent pulmonary infections. Thoracic endoscopy revealed a fragile, inflammatory, and granulomatous aspect of the bronchi. Amyloid deposits were observed in the upper digestive tract, salivary glands, temporal artery, and tracheobronchial tree. Symptomatic treatment was offered. Recurrent pulmonary infections occurred during the follow-up. Lung involvement in hereditary ALys has only been exceptionally described. Although vascular involvement has already been reported in ALys in many organs, it never concerned cranial arteries. This case highlights the systemic nature of the amyloid protein variant deposits and expands the spectrum of clinical manifestations to chest involvement. The literature review highlights that hereditary ALys with the p.Trp82Arg variant is frequent in patients coming from Piedmont (Italy). Due to diffuse organs involvement related to ALys, it is important not to misdiagnose ALys for AL amyloidosis, the most frequent form of amyloidosis.

Anaphylactic reaction to pemetrexed: a case report.

Pemetrexed is approved to treat non-small cell lung cancer and has an overall favorable toxicity profile. We describe a 58-year-old man who developped an anaphylactic shock within few minutes from the beginning of pemetrexed perfusion. Pemetrexed was discontinued and the patient's symptoms gradually resolved with administration of symptomatic treatment. Serum tryptase level remained normal and intra dermal skin tests were negative eventhough a nonspecific papule was noted. This case suggests that caution should be exercised when prescribing pemetrexed and clinicians must be warranted for the possibility of serious adverse events associated with pemetrexed use.

Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.

Acetylcholine (neuronal and non-neuronal origin) regulates bronchoconstriction, and mucus secretion. It has an inflammatory effect by inducing attraction, survival and cytokine release from inflammatory cells. Muscarinic receptors throughout the bronchial tree are mainly restricted to muscarinic M1, M2 and M3 receptors. Three long-acting muscarinic receptor antagonists (LAMAs) were approved for the treatment of chronic obstructive pulmonary disease (COPD) in Europe: once-daily tiotropium bromide; once-daily glycopyrronium bromide; and twice-daily aclidinium bromide. All have higher selectivity for M3 receptors than for M2 receptors, and dissociate more slowly from the M3 receptors than they do from the M2 receptors. Some LAMAs showed anti-inflammatory effects [inhibition of neutrophil chemotactic activity and migration of alveolar neutrophils, decrease of several cytokines in the bronchoalveolar lavage (BAL) including interleukin (IL)-6, tumor necrosis factor (TNF)-α and leukotriene (LT)B4] and antiremodeling effects (inhibition of mucus gland hypertrophy and decrease in MUC5AC-positive goblet cell number, decrease in MUC5AC overexpression). In the clinic, LAMAs showed a significant improvement of forced expiratory volume in 1 second (FEV1), quality of life, dyspnea and reduced the number of exacerbations in COPD and more recently in asthma. This review will focus on the three LAMAs approved in Europe in the treatment of chronic airway diseases.

Home-based respiratory rehabilitation in adult patients with moderate or severe persistent asthma.

OBJECTIVE: We assessed retrospectively the feasibility of a home-based respiratory rehabilitation (RR) program for asthmatics under optimal pharmacological treatment, as this type of care can reduce costs and offer a more patient-friendly approach for subjects with persistent asthma. METHODS: Fifty-two patients with persistent asthma were recruited to the RR program (20 males, 32 females, 54 ± 11 (SD) years, forced expiratory volume in one second 71 ± 33% of predicted mean value, BMI 29.9 ± 7.9 kg/m(2)). This two-month protocol comprised education sessions, respiratory physiotherapy and an exercise training program at home and in groups supervised by an adapted physical activity instructor. RESULTS: Thirty-nine patients completed the whole RR program, i.e. 25% dropout. The dropout rate was significantly higher with respect to younger patients in employment. The number of exacerbations decreased significantly during the year following the program, regardless of whether the patients had dropped out (p < 0.02) or not (p < 0.001). The distance walked during a 6-min walking test increased by 33 m (p < 0.001). Several indices measured during a cycle ergometer test increased significantly after RR: peak oxygen uptake (10%), oxygen uptake at ventilatory threshold (12%) and maximum load (19%), all at a similar maximum heart rate. Concerning quality of life assessment, the Short-Form-36 Item Health Survey revealed a non-significant improvement in the "health change" item after RR (p < 0.07). CONCLUSIONS: This study demonstrates the potential of a home-based program in the treatment and rehabilitation of patients with asthma. Both functional and physiologic indices improved during the follow-up period.

Lung cancer following bronchoscopic lung volume reduction for severe emphysema: a case and its management.

Bronchoscopic lung volume reduction using endobronchial valves has been suggested as a potentially safer alternative to surgery in selected cases. Complications of this technique include pneumothoraces, pneumonia, COPD exacerbations, hemoptysis, and valve migrations. We report the case of a male patient who developed a parenchymal mass in the treated lobe after valve insertion. Due to severe emphysema, transthoracic needle aspiration was not feasible. Removal of the valves was mandatory to perform transbronchialbiopsies which revealed a non-small cell primary lung cancer. This first description illustrates the potential risk of lung cancer development following bronchoscopic lung volume reduction and highlights the different approach to diagnosis and management of indeterminate peripheral lung lesions needed in this context.

[Definitions of asthma, assessment of disease severity and control]. / Définitions de l'asthme, evaluation de la sévérité et du contrôle.

The definitions of asthma are numerous, often descriptive and non evidences based. They have been used in the clinic to suspect, diagnose a condition which remains in 2011, more a syndrome than a disease. Acute severity, control and severity are current concepts to be used to evaluate a given patient at a given time. They should be better defined and understood to be used more appropriately. At present, these notions are often interchangeable in the literature, used without precisions and no real benefit for the patients and physicians. In the present review, we try to clarify the wording of definitions to be used in the daily practice including difficult asthma. Control of asthma is related to recent daily symptoms and exacerbations; it represents the ultimate goal of treatments according to current guidelines. Acute severe asthma represents the highest point of a severe exacerbation requiring a standardized management in emergency. Chronic severity refers to a longer period of time including the importance of the treatment to maintain a good or optimal control, as well as future risks. It is more linked to the natural history representing a marker of a persistent chronic disease.

An update on the efficacy and safety of aclidinium bromide in patients with COPD.

Aclidinium is a potent and selective muscarinic antagonist, which interacts rapidly with muscarinic receptors and shows subnanomolar affinity for the five human muscarinic receptors (M(1)-M(5)); its association rate for the M(3) receptor is similar to that of ipratropium and 2.6 times faster than that of tiotropium. Aclidinium dissociates slightly faster from M(2) and M(3) receptors than tiotropium but much more slowly than ipratropium. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Aclidinium undergoes rapid hydrolysis in the plasma into two major compounds, the alcohol (LAS34823) and the carboxylic acid (LAS34850) metabolites, resulting in low and transient systemic exposure to the active drug. The two major metabolites show no significant affinity for human muscarinic receptors. A potent bronchodilatory activity has been observed after inhaled administration of aclidinium. Clinical trials have provided evidence of sustained bronchodilation similar to that observed with tiotropium. Trial results have confirmed the positive safety profile of aclidinium, particularly in terms of a very low propensity to cause anticholinergic adverse events. Aclidinium is now moving to phase III clinical development for chronic obstructive pulmonary disease (COPD).

Unsuccessful rechallenge with pemetrexed after a previous radiation recall dermatitis.

Radiation recall dermatitis is characterized by an inflammatory reaction within a previously irradiated volume after administration of a drug. Antineoplastic drugs have mainly been involved in radiation recall reactions. This phenomenon is well known but poorly understood. Many hypotheses as stem-cell depletion in the radiotherapy field, heritable mutations within surviving stem cells, local vascular changes as well as a drug hypersensitivity reaction have been proposed to explain these reactions. In this report, we describe a non-small cell lung cancer patient treated with a carboplatin plus gemcitabine combination chemotherapy as first line followed by pemetrexed as second line therapy. Twenty-five years ago, she completed radiation therapy for breast cancer. Three days after the first cycle of pemetrexed, she presented with a radiation recall dermatitis. As EGFR-staining was negative, we rechallenged the patient with pemetrexed. Unfortunately, although less intense, we faced a recurrence of the skin reaction and pemetrexed was no longer continued.