https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)30879-6.pdf

After asthma: redefining airways diseases

https://www.cysticfibrosisjournal.com/article/S1569-1993(15)00058-2/pdf

Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy

https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(16)00023-0.pdf

Progress in Therapies for Cystic Fibrosis

Formerly regarded as a rare disease, bronchiectasis is now increasingly recognised and a renewed interest in the condition is stimulating drug development and clinical research. Bronchiectasis represents the final common pathway of a number of infectious, genetic, autoimmune, developmental and allergic disorders and is highly heterogeneous in its aetiology, impact and prognosis. The goals of therapy should be: to improve airway mucus clearance through physiotherapy with or without adjunctive therapies; to suppress, eradicate and prevent airway bacterial colonisation; to reduce airway inflammation; and to improve physical functioning and quality of life. Fortunately, an increasing body of evidence supports interventions in bronchiectasis. The field has benefited greatly from the introduction of evidence-based guidelines in some European countries and randomised controlled trials have now demonstrated the benefit of long-term macrolide therapy, with accumulating evidence for inhaled therapies, physiotherapy and pulmonary rehabilitation. This review provides a critical update on the management of bronchiectasis focussing on emerging evidence and recent randomised controlled trials.

https://erj.ersjournals.com/content/erj/45/5/1446.full.pdf

Management of bronchiectasis in adults

Chronic lower airway infection with Pseudomonas aeruginosa is a major contributor to morbidity and mortality in individuals suffering from the genetic disease cystic fibrosis (CF). Whereas it was long presumed that each patient independently acquired unique strains of P. aeruginosa present in their living environment, multiple studies have since demonstrated that shared strains of P. aeruginosa exist among individuals with CF. Many of these shared strains, often referred to as clonal or epidemic strains, can be transmitted from one CF individual to another, potentially reaching epidemic status. Numerous epidemic P. aeruginosa strains have been described from different parts of the world and are often associated with an antibiotic-resistant phenotype. Importantly, infection with these strains often portends a worse prognosis than for infection with nonclonal strains, including an increased pulmonary exacerbation rate, exaggerated lung function decline, and progression to end-stage lung disease. This review describes the global epidemiology of clonal P. aeruginosa strains in CF and summarizes the current literature regarding the underlying biology and clinical impact of globally important CF clones. Mechanisms associated with patient-to-patient transmission are discussed, and best-evidence practices to prevent infections are highlighted. Preventing new infections with epidemic P. aeruginosa strains is of paramount importance in mitigating CF disease progression.

Epidemiology, Biology, and Impact of Clonal Pseudomonas aeruginosa Infections in Cystic Fibrosis.

https://www.cysticfibrosisjournal.com/article/S1569-1993(13)00238-5/pdf

A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis

Objective: To assess the bioequivalence of 10 mg dapagliflozin tablets compared with that of 10 mg Farxiga® (dapagliflozin) tablets of AstraZeneca Pharmaceuticals LP, USA in healthy, adult volunteers under fasting conditions. Materials and Methods: This was an open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover, oral bioequivalence study. Volunteers were randomized to receive either test product or reference product of 10 mg dapagliflozin tablets under the fasting condition with a nine-day washout period. The primary pharmacokinetic (PK) parameters were maximum plasma concentration (Cmax), area under the curve (AUC) at time t (AUCt), and AUC extrapolated to infinity (AUCinf). Adverse events were assessed as safety endpoints. The bioequivalence was assessed to evaluate that the two formulations are not different from one another if the 90% confidence interval for the ratio of the geometric least square means falls completely within the predefined range of 80–125%. Results: Fifty-two healthy adult volunteers were randomized, and 47 completed the study. The mean values for Cmax, AUCt, and AUCinf were almost identical for test and reference products after administration to healthy human volunteers under fasting conditions. A total of 14 adverse events were reported by 10 volunteers during the study. All adverse events were mild to moderate in nature and did not cause study withdrawal. Conclusion: The test product dapagliflozin 10 mg was bioequivalent with the reference product in healthy, adult, human volunteers under fasting conditions. The availability of the affordable generic dapagliflozin has the potential to improve clinical outcomes in millions of patients in India because of its renoprotective, cardioprotective, and glucose-lowering effects.

Bioequivalence study of two different dapagliflozin tablet formulations in healthy adult Indian volunteers

Objective: The objective was to evaluate the clinical experience and treatment patterns of generic dapagliflozin usage in different patient profiles in Indian settings. Materials and Methods: A retrospective, multicentric, real-world study included patients with type 2 diabetes mellitus (T2DM) (aged >18 years), inadequately controlled by existing antidiabetic therapy and receiving generic dapagliflozin as an add-on to existing oral antidiabetic drug(s) with or without insulin or switch therapy. Baseline characteristics and treatment-related outcomes were retrieved from the medical records and analyzed. Results: A total of 1935 patients were included, of which 1279 (66.1%) were males. The mean age was 57.4 years, and around half of the patients (51.4%) were aged from 45 to 60 years. Hypertension (55.9%) and dyslipidemia (19.8%) were the common comorbidities. The majority (n = 1122; 60%) of patients received dapagliflozin in combination with one or two antihyperglycemic drugs. More than half of the patients received metformin (56.8%) or sulfonylurea (52.3%) in combination with dapagliflozin. A dose of 10 mg (93.4%) was the most commonly used dose of dapagliflozin. The mean levels of glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose were significantly reduced to 1.1% (1.0–1.1), 30.5 mg/dL (29.2–31.9), and 57.5 mg/dL (55.1–59.9), respectively, after the initiation of dapagliflozin. A total of 1935 patients experienced weight changes during the treatment, of which 90.5% of patients showed weight loss. Hypoglycemic events were reported in 12.5% of patients. Physician global evaluation of efficacy and tolerability showed a majority of patients on a good-to-excellent scale (97.3% and 97.1%). Conclusion: Generic dapagliflozin showed a significant improvement in glycemic parameters and reduced body weight with low hypoglycemic events. The administration of dapagliflozin provided a good-to-excellent efficacy and tolerability profile in patients with T2DM. To the best of our knowledge, this is the first study confirming the efficacy, safety, and usefulness of generic dapagliflozin in patients with T2DM.

S. Bhattacharya

Papers

A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis

Bioequivalence study of two different dapagliflozin tablet formulations in healthy adult Indian volunteers

Real-world evidence of generic dapagliflozin: Relevance and results from Indian multicenter retrospective study

Real-world assessment of effectiveness and safety profile of remogliflozin etabonate in management of type 2 diabetes mellitus