Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease: Research outline and call for collaboration.

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.

Outcomes of Antibiotics in Adults with "Difficult to Treat" Asthma or the Overlap Syndrome.

PURPOSE: Macrolides are a recommended treatment option for severe asthma, but data for "difficult-to-treat" asthma, the asthma-COPD "overlap" syndrome, and treatment duration beyond one year are lacking. We present long-term data from community practice experience providing insights for practice and research. METHODS: We report data from (1) baseline (pre-treatment) chart review of antibiotic-treated asthma patients and (2) follow-up telephone interviews documenting severe exacerbations (NIH criteria), Asthma Control Test (ACT) scores, and asthma controller use at baseline and follow-up, analyzed using a "before-after" model. RESULTS: A total of 101 patients (mean age 55.6 years (Sd 16.8), 66 females) were included. None had ever taken high dose inhaled corticosteroids and 79 (78.2%) were severely uncontrolled (ACT score ≤15) before treatment. Coexisting COPD was present in 62 (61.4%) patients. Azithromycin or azithromycin plus doxycycline was primarily prescribed with a median treatment duration of 12 months and median follow-up duration of 22 months. Severe exacerbations in the month before treatment occurred in 50.5% vs 17.8% at follow-up (P<0.0001). Mean ACT score increased from 12.2 to 20.6 (P<0.0001). The number of patients taking controller medications decreased (P<0.0001 for inhaled corticosteroids; P<0.001 for long-acting beta agonist/long-acting muscarinic antagonist; P<0.05 for leukotriene receptor antagonists). Of the 79 severely uncontrolled patients, 51 (64.6%) became controlled at follow-up, and of these 51, 27 (52.9%) continued to take antibiotics while 24 (47.1%) had discontinued antibiotics earlier yet remained controlled. CONCLUSION: Antibiotic treatment may be beneficial in a significant proportion of "difficult to treat" asthma patients beyond one year, including some patients with the overlap syndrome and/or who fail to meet criteria for refractoriness.