tiotropium-bromide and Eosinophilia

The aim of this manuscript is to outline an approach to severe asthma, which is among the most challenging problems faced by paediatric pulmonologists. A logical, protocolised approach is essential. The first step is to rule out alternative diagnoses. The next step is a multidisciplinary assessment. Severe, therapy resistant asthma (STRA) is rare, and most of those referred will improve if basic management is corrected, especially adherence to treatment. However some are unable or unwilling to make necessary changes (refractory asthma plus or refractory difficult asthma). Some, especially asthma in the obese, and those thought to have STRA, progress to bronchoscopic airway phenotyping and a parenteral steroid trial to determine an individualised treatment plan. Those with persistent eosinophilc airway inflammation should be considered for omalizumab, and mepolizumab. Pauci-inflammatory asthma remains a therapeutic challenge, with a paucity of evidence; increasing steroid therapy seems neither logical nor efficacious, but options include tiotropium and azithromycin. However the most important message to the paediatrician looking after a child with apprently severe asthma is that the answer is not uncritically escalating treatment, but finding the answer to the question, what is it about this child, and his/her environment, which means there is no response to what should be easily treated airway pathology? The answer usually requires input from a skilled and experienced multi-disciplinary team, without which management is unlikely to be succesful. CONCLUSION: When managing a child with severe asthma, a detailed multi-disciplinary is essential to get the basic management right, before prescribing biologicals.

Topics: Algorithms; Allergens; Anti-Asthmatic Agents; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Asthma; Asthma, Exercise-Induced; Azithromycin; Bronchodilator Agents; Bronchoscopy; Child; Comorbidity; Environmental Exposure; Eosinophilia; Glucocorticoids; Humans; Medication Adherence; Obesity; Omalizumab; Patient Care Team; Severity of Illness Index; Smoking; Tiotropium Bromide; Tobacco Smoke Pollution

Exacerbations of persistent or intermittent asthma should be anticipated by physicians and health-care professionals. Patients who are likely to experience an exacerbation often have a history of an exacerbation in the previous year, and the absolute eosinophil count in peripheral blood is ≥ 400/μL. Similarly, expectorated or induced sputum eosinophilia of ≥2% is associated with exacerbations. These phenotypic findings have led to effective biologic therapies, which target eosinophils or immunoglobulin E or the T-helper type 2 phenotype, especially in children, adolescents, and adults with frequent exacerbations. In children, a reduced forced expiratory volume in the first second of expiration (FEV

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Budesonide; Child; Clinical Trials as Topic; Eosinophilia; Forced Expiratory Volume; Humans; Sputum; Surveys and Questionnaires; Tiotropium Bromide

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Allergens; Anti-Asthmatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Bronchial Thermoplasty; Bronchodilator Agents; Environmental Exposure; Eosinophilia; Humans; Practice Guidelines as Topic; Prenatal Care; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Tiotropium Bromide; Vitamin D; Vitamins

Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide. Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia. This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.

Topics: Adrenal Cortex Hormones; Allergens; Animals; Bronchodilator Agents; Budesonide; Cholinergic Antagonists; Eosinophilia; Extracellular Matrix; Glucocorticoids; Guinea Pigs; Humans; Hypersensitivity; Inflammation; Male; Muscle, Smooth; Ovalbumin; Scopolamine Derivatives; Tiotropium Bromide; Trachea