Effects of Air Pollution on Adults with Chronic Obstructive Pulmonary Disease

Few studies have been conducted on the effects of air pollution on patients with chronic obstructive pulmonary disease (COPD). During a 14-mo period, 39 Parisian adults with severe COPD were monitored by their physicians. Daily levels of 4 air pollutants were provided by an urban air-quality network. Exacerbation of COPD was associated only with ozone (O₃) (odds ratio [OR] = 1.44 for a 10-μg/m³ increase in O₃; 95% confidence interval [Cl] = 1.14, 1.82), with a lag of 2-3 days. The effect of O₃ was greater in patients whose carbon dioxide pressure (PaCO₂) was higher than 43 mm Hg (OR = 1.83; 95% Cl = 1.36, 2.47) vs. those with a lower PaCO₂ (OR = 1.26; 95% Cl = 0.90, 1.77). The effect of O₃ was unchanged, regardless of the maintenance medications used. The only air pollutant to which patients with severe COPD were particularly sensitive was O₃.     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.     

Mycoplasma genitalium,an agent of reemerging sexually transmitted infections

M. genitalium is a reemerging microorganism, responsible for sexually transmissible infections (STIs), with prevalence which varies depending on the country and population group studied. We report here M. genitalium prevalence among the specimens received for STI diagnosis in our routine microbiological laboratory in the university hospital in Marseille, France. We tested 4 624 samples from 3 793 patients using qPCR for M. genitalium, C. trachomatis, N. gonorrheae, T. pallidum. Of these samples, 528 (13.6%) patients were tested positive for at least one pathogen and 126 (3.3%) were positive for M. genitalium. M. genitalium is the second most prevalent micro‐organism detected in women after C. trachomatis (10.4%) and the third most prevalent in men after C. trachomatis (5.1%) and N. gonorrhoeae (4.4%). We observed no significant differences between the prevalence of M. genitalium in vaginal, urethral and urine specimens (p = 0.9). Prevalence of M. genitalium is significantly higher in patients aged between 10–30 years (4.1%) compared to those aged between 30 and 50 years (2.7%) (p = 0.02, RR = 1.54 [1.06–2.24]) and patients over 50 years of age (1.1%) (p = 0.003, RR= 3.98 [1.47–10.8]). M. genitalium is a common agent of STI, therefore we suggest that this micro‐organism should be systematically tested during chronic, recurrent, or antibiotic resistant genital infections and in populations at high‐risk of STIs.     

Deletion of the Uracil Permease Gene Confers Cross-Resistance to 5-Fluorouracil and Azoles in Candida lusitaniae and Highlights Antagonistic Interaction between Fluorinated Nucleotides and Fluconazole

We characterized two additional membrane transporters (Fur4p and Dal4p) of the nucleobase cation symporter 1 (NCS1) family involved in the uptake transport of pyrimidines and related molecules in the opportunistic pathogenic yeast Candida lusitaniae. Simple and multiple null mutants were constructed by gene deletion and genetic crosses. The function of each transporter was characterized by supplementation experiments, and the kinetic parameters of the uptake transport of uracil were measured using radiolabeled substrate. Fur4p specifically transports uracil and 5-fluorouracil. Dal4p is very close to Fur4p and transports allantoin (glyoxyldiureide). Deletion of the FUR4 gene confers resistance to 5-fluorouracil as well as cross-resistance to triazoles and imidazole antifungals when they are used simultaneously with 5-fluorouracil. However, the nucleobase transporters are not involved in azole uptake. Only fluorinated pyrimidines, not pyrimidines themselves, are able to promote cross-resistance to azoles by both the salvage and the de novo pathway of pyrimidine synthesis. A reinterpretation of the data previously obtained led us to show that subinhibitory doses of 5-fluorocytosine, 5-fluorouracil, and 5-fluorouridine also were able to trigger resistance to fluconazole in susceptible wild-type strains of C. lusitaniae and of different Candida species. Our results suggest that intracellular fluorinated nucleotides play a key role in azole resistance, either by preventing azoles from targeting the lanosterol 14-alpha-demethylase or its catalytic site or by acting as a molecular switch for the triggering of efflux transport.