Meta-analysis and cost-effectiveness analysis of intranasal corticosteroid treatment in allergic rhinitis with ocular symptoms.

BACKGROUND: Intranasal corticosteroid (INCS) has a beneficial effect on ocular symptoms in allergic rhinitis (AR). To our knowledge, the cost-effectiveness of available INCS for AR with ocular symptoms is yet to be demonstrated. OBJECTIVE: To evaluate the cost-effectiveness of INCSs including Budesonide (BANS), Mometasone furoate (MFNS), Triamcinolone (TANS), and Fluticasone furoate (FFNS) on ocular symptoms associated with AR in the Thai context. METHODS: The percentage of effectiveness in improving total ocular symptoms score (TOSS) was derived from the result of a meta-analysis that estimated the SMD of each INCS treatment compared to placebo as clinical input parameters. A cost-effectiveness analysis based on a decision-tree model to assess one-year costs and outcomes from a Thai societal perspective. The outcomes were to compare incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analyses (PSA) were also conducted to capture parameter uncertainties. RESULTS: 13 eligible RCTs with a total of 3,722 patients with SAR were included in the analysis. The percentage of effectiveness of FFNS, MFNS, TANS, and BANS was 59.89%, 45.60%, 24.89%, and 16.00%, respectively. The ICER of FFNS, MFNS, and TANS is THB-6,539.92, 4,593.83, and 1,401.24 compared to BANS. CECA result showed the probability of using FFNS is considered cost-effective in 87.50% of cases from zero value followed by MFNS (0.80%), TANS (5.40%), and BANS (6.30%). With a threshold greater than THB20,000, FFNS is considered a cost-effective strategy. CONCLUSIONS: FFNS is a cost-effective option compared to alternative INCSs in Thailand for treating AR with ocular symptoms.

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach.

INTRODUCTION: Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade 2) versus severe and very severe COPD (GOLD grades 3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD. METHODS: The modelling approach used data on decline in forced expiratory volume in 1 s (FEV1) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV1 and annual exacerbation rates from age 40 to 75 years in COPD with initiation of long-acting anti-muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65 years of age. RESULTS: Model-predicted decline in FEV1 showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65 years preserved an additional 469.7 mL or 236.0 mL, 327.5 mL or 203.3 mL, or 213.5 mL or 137.5 mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65 years of age, respectively. CONCLUSIONS: This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA.

Pharmacology Versus Convenience: A Benefit/Risk Analysis of Regular Maintenance Versus Infrequent or As-Needed Inhaled Corticosteroid Use in Mild Asthma.

INTRODUCTION: This study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma. METHODS: A pharmacokinetic/pharmacodynamic model was developed and validated describing the relationship between ICS dose and time-course for airway bronchoprotection, [provocative concentration of adenosine monophosphate (AMP) causing ≥ 20% decline in forced expiratory volume in 1 s (FEV1) (AMP PC20)], for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD). For regular ICS maintenance therapy (100% and 50% adherence) and infrequent or as-needed use (dosing 3-4 times per week), treatment effectiveness was expressed as percent time during 28 days when bronchoprotection exceeded either the threshold for a treatment-related bronchoprotective effect (AMP PC20 ≥ 0.25 doubling dose) or the threshold for a clinically significant bronchoprotective effect (AMP PC20 ≥ 1.0 doubling dose). This value was divided by the total ICS dose administered expressed in prednisolone equivalents to give a therapeutic index (TI). RESULTS: The model-predicted time course of ICS-induced bronchoprotection with regular daily maintenance dosing and 100% adherence showed that all ICS at the highest recommended doses for mild asthma exceeded the threshold for clinically significant bronchoprotective effect for all or most of the 28-day dosing period, mean (90% CI); 100% (96.1-100), 99.9% (8.0-100) and 100% (58.2-100) with TI values of 16.9, 6.6 and 5.4 for FF 100 µg OD, FP 200 µg BID and BUD 200 µg BID, respectively. For simulated poor adherence (50%) to regular daily maintenance therapy, corresponding mean (90% CI) values were; 75.7% (39.4-89.1), 52.3% (0.7-69.2) and 51.3% (28.6-58.3) with TI values of 25.7, 6.9 and 5.6. For simulated infrequent/as needed use the corresponding values were; 77.0% (37.6-87.0), 25.5% (0.0-38.0) and 26.2% (14.3-31.5) with TI values of 26.1, 6.7 and 5.7. For all regimen/scenarios, FF had the most sustained efficacy and favourable TI followed by FP and BUD. CONCLUSIONS: At doses recommended for mild asthma, all ICS regimens provide sustained bronchoprotective efficacy when dosed regularly with high adherence. With poor adherence or use 3-4 times per week (infrequent/as needed), longer-acting ICS molecules will more likely provide sustained protection and a better TI versus shorter duration of action molecules (FF > FP ≥ BUD). These data highlight the benefits of using ICS as regular daily maintenance dosing in mild asthma and the potential risks of under-treatment with ICS (which may occur with ICS/formoterol as-needed approach in mild persistent asthma) associated with reduced levels of bronchoprotection.

Understanding perception of chronic obstructive pulmonary disease among general practitioners, physicians, and pulmonologists in India: Results from a face-to-face survey.

BACKGROUND: Challenges exist in the diagnosis, management and follow-up of patients with chronic obstructive pulmonary disease (COPD) in India. Lack of awareness of the disease, its symptoms and its implications may significantly contribute in preventing individuals with symptoms from seeking advice from their primary care physicians or eliminating risk factors. This cross-sectional survey aimed to explore the attitudes, beliefs, and knowledge of doctors (general practitioners [GPs], physicians and pulmonologists) related to COPD recognition, diagnosis, and treatment in India. METHODS: Data was collated from 91 randomly selected GPs, physicians and pulmonologists through a questionnaire and face-to-face interviews, in 8 cities of India. RESULTS: The response rate to the survey was 68% (61 out of 91). Majority of the doctors (90% of GPs-physicians and 82% of pulmonologists) reported that patients with COPD visit them at moderate to severe stages of the disease. 44% of the GPs and physicians reported that they had never performed spirometry to make a diagnosis of COPD. About 35% of doctors reported that COPD occurred only in smokers. The most common reported barriers to the treatment of COPD were difficulty in explaining COPD to the patients, poor patient compliance to the prescribed treatment and the inability of patients to give up smoking. Most doctors agreed that compliance with treatment is a major concern in patients with COPD due to an ageing population, existence of limited therapeutic options and presence of comorbidities. CONCLUSION: The results of this cross-sectional survey of doctors in India, highlighted the need for increasing the awareness about COPD at both doctor and patients level to overcome the prevalent under-diagnosis and under-treatment in COPD.

Mounier-Kuhn syndrome: report of 8 cases of tracheobronchomegaly with associated complications.

Mounier-Kuhn syndrome is a rare congenital abnormality characterized by atrophy or absence of elastic fibers and thinning of smooth muscle layer in the trachea and main bronchi. These airways are thus flaccid and markedly dilated on inspiration and collapsed on expiration. First- to fourth-order bronchi are affected. There is an increase in dead space, tidal volume and diminished clearing of secretions. The usual presentation is recurrent respiratory tract infections with a broad spectrum of functional impairment ranging from minimal disease with preservation of lung function to severe disease in the form of bronchiectasis, emphysema and pulmonary fibrosis, ultimately culminating in respiratory failure and death. A congenital connective tissue weakness, in combination with inhalation of irritants like cigarette smoke and air pollution, are raised as possible factors in the development of this syndrome. Eight cases of tracheobronchomegaly with its associated complications are reported. Computed tomography scan of the chest was used for the diagnosis of tracheobronchomegaly. Treatment is mainly supportive with chest physiotherapy and antibiotics; however, there are a few reported cases where insertion of a tracheal stent resulted in some success.

Influence of spinal deformity on pulmonary function, arterial blood gas values, and exercise capacity in thoracic kyphoscoliosis.

OBJECTIVE: To evaluate the influence of thoracic spine curvature on lung parameters in kyphoscoliosis. METHODS: Twenty-one patients with kyphoscoliosis were evaluated at the Vallabhbhai Patel Chest Institute, Delhi, India from January to June 2006 using spirometry, arterial blood gas (ABG), and 6-minute walk test. The degree of spinal deformity was measured by Cobb`s method for angle of scoliosis and angle of kyphosis. RESULTS: There were 13 males and 8 females (mean age 47.38+/-20.10 years). Decreased lung volumes, hypoxemia, arterial oxygen desaturation, and decreased exercise capacity was observed in patients with kyphoscoliosis. The angle of scoliosis ranged from 60-126 degrees (78.1+/-18.3) and angle of kyphosis ranged from 5-48 degrees (18.05+/-10.5). The forced vital capacity (FVC) was 1.92+/-0.8 L (0.66-3.44), and the forced expiratory volume in one second (FEV1) was 1.51+/-0.5 L (0.6-2.6). The FEV1/FVC was 60.9+/-12.9 (42-86%). The partial arterial oxygen tension was 51.7+/-6.9 Hg. The partial pressure of carbon dioxide in arterial blood was 49.85+/-7.9 mm Hg. The functional oxygen saturation was 84+/-3.7%. No correlation was found between pulmonary function test (PFT) or ABG values with the degree of spinal deformity. Mean oxygen desaturation (87.48-84.43%) and rise in systolic blood pressure (118.48-126.67 mm Hg) during walk test correlated well with degree of spinal deformity. CONCLUSION: The severity of pulmonary impairment could not be inferred from the angle of scoliosis alone. The 6-minute walk test gives an early indication of limitations and correlates well with structural deformity. The PFT and ABG parameters do not correlate well with the severity of deformity. Thus, the 6-minute walk test must be included in the thorough evaluation of all patients with kyphoscoliosis.