Precision medicine in united airways disease: A "treatable traits" approach.

United airways disease (UAD) is the concept that the upper and lower airways, which are anatomically and immunologically related, form a single organ. According to this concept, upper and lower airway diseases are frequently comorbid because they reflect manifestations of a single underlying disease at different sites of the respiratory tract. Allergic asthma-allergic rhinitis is the archetypal UAD, but emerging data indicate that UAD is a heterogeneous condition and consists of multiple phenotypes (observable clinical characteristics) and endotypes (pathobiologic mechanisms). The UAD paradigm also extends to myriad sinonasal diseases (eg, chronic rhinosinusitis with or without nasal polyps) and lower airway diseases (eg, bronchiectasis, chronic obstructive pulmonary disease). Here, we review currently known phenoendotypes of UAD and propose a "treatable traits" approach for the classification and management of UAD, wherein pathophysiological mechanisms and factors contributing to disease are identified and targeted for treatment. Treatable traits in UAD can be analyzed according to a framework comprising airway inflammation (eosinophilic, neutrophilic), impaired airway mucosal defense (impaired mucociliary clearance, antibody deficiency), and exogenous cofactors (allergic sensitizers, tobacco smoke, microbes). Appreciation of treatable traits is necessary in advancing the effort to deliver precise treatments and achieve better outcomes in patients with UAD.

Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma.

BACKGROUND: Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. OBJECTIVES: To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: November 2006. SELECTION CRITERIA: All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist. DATA COLLECTION AND ANALYSIS: In original review, two reviewers independently assessed trial quality and extracted data, similarly in this update two reviewers undertook this. Study authors were contacted for additional information. MAIN RESULTS: Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV(1) predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI 0.30 to 0.63, Risk Difference -0.11; 95% CI -0.16 to -0.07, Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95% CI 0.29 to 0.86, Risk Difference -0.07; 95% CI -0.12 to -0.02, NNT 14; 95% CI 8 to 50) and gastrointestinal adverse events (Relative Risk 0.30; 95% CI 0.17 to 0.55, Risk Difference -0.11; 95% CI -0.16 to -0.06, NNT 9; 95% CI 6 to 16). AUTHORS' CONCLUSIONS: Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Endoscopic ultrasound-guided fine needle aspiration in the evaluation of suspected lung cancer.

BACKGROUND AND AIM: The role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis and staging of lung cancer is still not fully explored. This prospective study aimed to define the effectiveness of EUS-FNA as an adjunct to computer tomography (CT) and bronchoscopy in the evaluation of suspected lung cancer in routine clinical practice. METHODS: Over a period of 20 weeks, the data of 16 consecutive patients suspected of lung cancer on account of respiratory symptoms, and/or the findings of either a mass or mediastinal lymph nodes on helical CT, who were referred for evaluation by EUS, were prospectively collected. Fourteen of these patients underwent sequential bronchoscopy followed by EUS-FNA in the same setting. RESULTS: Bronchoscopy was performed in 15 patients, while EUS was performed in all 16 patients. Bronchoscopy diagnosed 9 cases of non-small-cell lung cancer (NSCLC) but was falsely negative in 3 cases of malignancies, which were all established by EUS-FNA of mediastinal lymph nodes (2 cases of NSCLC and 1 case of esophageal squamous cell cancer). EUS-FNA also diagnosed advanced NSCLC in another patient who did not undergo bronchoscopy, such that eventually 13 patients were diagnosed to have malignancies. Distant metastases were diagnosed by EUS-FNA in 4 cases of NSCLC (2 cases of left adrenal gland and 2 cases of pancreatic metastases). Two patients were diagnosed to have sarcoidosis and 1 patient was diagnosed to have pneumoconiosis eventually. CONCLUSIONS: EUS-FNA is useful as an adjunct to CT and bronchoscopy in the evaluation of suspected lung cancer.

Dapsone hypersensitivity syndrome masquerading as a viral exanthem: three cases and a mini-review.

INTRODUCTION: We report 3 cases of dapsone hypersensitivity syndrome due to anti-malarial chemoprophylactic treatment with maloprim, in military servicemen, presenting like a viral exanthem. CLINICAL PICTURE: Three male military recruits presented with fever and rash, 6 to 8 weeks after commencing on weekly doses of maloprim. TREATMENT: A course of topical and systemic corticosteroids and oral antihistamines were started. OUTCOME: All cases showed gradual resolution of fever, rash and eventual normalisation of liver function test. CONCLUSION: A high index of suspicion was required before this uncommon syndrome can be recognised. Early institution of corticosteroid therapy and discontinuation of maloprim are the mainstays of treatment.