BACKGROUND: Exposure to airborne fungi has been related with exacerbation of asthma in adults and children leading to increased outpatient, emergency room visits, and hospitalizations. Hypersensitivity to these airborne fungi may be an important initial predisposing factor in the development and exacerbation of asthma. OBJECTIVE: This study was conducted to determine an association between fungal types and spore concentrations with the risk of asthma exacerbation in adults. METHODS: This cross-sectional study was conducted from May 2008 to August 2009 at the Aga Khan University Hospital Karachi, Pakistan. All adult (age≥16 years) patients presenting to the hospital with acute asthma exacerbation were enrolled after informed consent. A home survey was conducted for each patient to assess their environmental characteristics. Indoor air samples were also obtained from the patient's home to determine the type and spore concentration of fungi within the week of their enrollment in the study. RESULTS: Three hundred and ninety-one patients with an acute asthma exacerbation were enrolled during the study period. The mean age of participants was 46 years (standard deviation, ±18 years) and 247 (63.2%) were females. A trend of higher asthma enrollment associated with higher Aspergillus concentrations was found in two consecutive summers. A total of nineteen types of fungi were found in air samples. Aspergillus spp. was the most frequently isolated fungus with acute asthma exacerbation. CONCLUSION: An association of higher concentration of indoor Aspergillus spp. with asthma exacerbation in adults was observed in this study.
Adult ; Aspergillus ; Asthma ; Causality ; Child ; Cross-Sectional Studies ; Emergency Service, Hospital ; Female ; Fungi ; Hospitalization ; Humans ; Hypersensitivity ; Informed Consent ; Outpatients ; Pakistan ; Spores ; Spores, Fungal

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Toll-like receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.