Brief Report: Association Between Pain, Pulmonary Function, and Respiratory Symptoms in People With HIV.

BACKGROUND: People with HIV (PWH) experience chronic pain and respiratory symptoms, which are closely related in the general population. Pain may affect the impaired pulmonary function seen in PWH beyond its association with HIV alone. Our objective was to investigate the relationship of pain severity to pulmonary function, respiratory symptoms, and sleep disturbance in PWH. SETTING: Study sites included the University of Pittsburgh, University of California San Francisco, and University of Washington. METHODS: Pain, dyspnea, and sleep were assessed using the Brief Chronic Pain Questionnaire, St. George's Respiratory Questionnaire, and Pittsburgh Sleep Quality Index. Participants performed prebronchodilator and postbronchodilator spirometry and 6-minute walk test. Associations between pain severity, lung function, dyspnea, and sleep were assessed with bivariate and multiple quantile regression analysis adjusted for age, sex, race, body mass index, and smoking status. RESULTS: Of 159 PWH, the median age was 56 years with 30.8% women. Two-thirds experienced pain in the past week, with 40.3% reporting chronic pain. Pain severity was higher with female sex (P = 0.038), non-White race (P = 0.005), current smoking (P = 0.003), and lower CD4+ count (P = 0.035). In adjusted analysis, higher pain severity was correlated with reduced postbronchodilator forced expiratory volume in 1 second %predicted (P = 0.008), reduced postbronchodilator forced vital capacity %predicted (P = 0.019), and chronic obstructive pulmonary disease (P = 0.032). Greater pain severity was strongly associated with a higher St. George's Respiratory Questionnaire score (P < 0.001) and sleep disturbance (P < 0.001). CONCLUSIONS: In PWH, pain is common and associated with airflow obstruction, dyspnea, and sleep disturbance. Future studies assessing pain severity and pulmonary function over time could clarify the direction of this association and the impact on quality of life.

Association Between Inflammatory Pathways and Phenotypes of Pulmonary Dysfunction Using Cluster Analysis in Persons Living With HIV and HIV-Uninfected Individuals.

BACKGROUND: Persons living with HIV (PLWH) are at risk of developing different phenotypes of chronic lung disease, including chronic obstructive pulmonary disease. Mechanisms underlying these phenotypes are unclear. OBJECTIVE: To identify clusters of peripheral inflammatory mediators associated with pulmonary function to determine inflammatory pathways and phenotypes of chronic obstructive pulmonary disease in PLWH and HIV-uninfected individuals. METHODS: Study participants were PLWH and HIV-uninfected individuals enrolled in the Pittsburgh HIV Lung Cohort. Pulmonary function tests were performed for all participants. Chest computed tomographic scans were performed in a subset of PLWH. Plasma levels of 19 inflammatory mediators were measured by Luminex or ELISA. Clusters were identified based on the expression pattern of inflammatory mediators in PLWH and HIV-uninfected individuals, and the relationships among clinical parameters were evaluated within clusters by using cluster and network analyses. RESULTS: In PLWH, we identified a distinct cluster with higher levels of Th1, Th2, and Th17 inflammatory mediators with increased complexity of these mediators and inferred presence of pathogenic Th17 cell types. Individuals in this cluster had worse airway obstruction and more radiographic emphysema. In HIV-uninfected individuals, a cluster with high-grade systemic inflammation also had worse diffusing capacity for carbon monoxide. CONCLUSIONS: Inflammatory pathways associated with pulmonary dysfunction in PLWH suggest multifaceted immune dysregulation involved in different phenotypes of pulmonary dysfunction with a potential specific contribution of the Th17 pathway to airway obstruction in PLWH. Identification of these associations may help in development of treatments that could alter the course of the disease.

Factors Associated With Progression of Lung Function Abnormalities in HIV-Infected Individuals.

BACKGROUND: HIV is an independent risk factor for chronic obstructive pulmonary disease; however, baseline risk factors for lung function decline remain largely unknown in this population. METHODS: HIV-infected participants in the Pittsburgh Lung HIV Cohort with at least 3 pulmonary function measurements between 2007 and 2016 were included. Pulmonary function testing including postbronchodilator (BD) spirometry and diffusion capacity for carbon monoxide (DLco) was performed every 18 months. We used a mixed-effect linear model to evaluate factors associated with pulmonary function testing and DLco decline and logistic regression models to evaluate factors associated with rapid FEV1 decline (defined as >80 mL per year) and any DLco decline. RESULTS: Two hundred eighty-five HIV-infected participants were included. Median baseline CD4 cell count was 521 cells per micro liter, 61.9% had an undetectable HIV viral load at baseline, and 78.5% were receiving ART. Approximately 20% of participants met Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for a diagnosis of chronic obstructive pulmonary disease at baseline. Older age and baseline GOLD stage 1 compared with stage 0 were associated with faster decline in post-BD FEV1%, whereas female sex was associated with slower decline. Similarly, female sex was associated with slower decline in DLco%. HIV-related factors including CD4 cell count, viral load, and ART use were not significantly associated with pulmonary function decline. CONCLUSIONS: Older age, male sex, and higher baseline GOLD stage were associated with more rapid post-BD FEV1% decline in HIV-infected individuals.

High Prevalence of Pneumocystis jirovecii Dihydropteroate Synthase Gene Mutations in Patients with a First Episode of Pneumocystis Pneumonia in Santiago, Chile, and Clinical Response to Trimethoprim-Sulfamethoxazole Therapy.

Mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis jirovecii are associated with the failure of sulfa prophylaxis. They can develop by selection in patients receiving sulfa drugs or be acquired via person-to-person transmission. DHPS mutations raise concern about the decreasing efficacy of sulfa drugs, the main available therapeutic tool for Pneumocystis pneumonia (PCP). The prevalence of Pneumocystis DHPS mutations was examined in Pneumocystis isolates from 56 sulfa-prophylaxis-naive adults with a first episode of PCP from 2002 to 2010 in Santiago, Chile. Their clinical history was reviewed to analyze the effect of these mutations on response to trimethoprim-sulfamethoxazole (TMP-SMX) therapy and outcome. Mutant genotypes occurred in 22 (48%) of 46 HIV-infected patients and in 5 (50%) of 10 HIV-uninfected patients. Compared to patients with a wild-type genotype, those with mutant genotypes were more likely to experience sulfa treatment-limiting adverse reactions and to have a twice-longer duration of mechanical ventilation if mechanically ventilated. Specific genotypes did not associate with death, which occurred in none of the HIV-infected patients and in 50% of the non-HIV-infected patients. Chile has a high prevalence of DHPS mutations, which were presumably acquired through interhuman transmission because patients were not on sulfa prophylaxis. These results contrast with the low prevalence observed in other Latin American countries with similar usage of sulfa drugs, suggesting that additional sources of resistant genotypes may be possible. The twice-longer duration of mechanical ventilation in patients with mutant DHPS genotypes suggests a decreased efficacy of TMP-SMX and warrants collaborative studies to assess the relevance of DHPS mutations and further research to increase therapeutic options for PCP.

HIV infection is associated with diffusing capacity impairment in women.

Respiratory dysfunction is common with HIV infection, but few studies have directly assessed whether HIV remains an independent risk factor for pulmonary function abnormalities in the antiretroviral therapy era. Additionally, few studies have focused on pulmonary outcomes in HIV+ women. We tested associations between risk factors for respiratory dysfunction and pulmonary outcomes in 63 HIV+ and 36 HIV-uninfected women enrolled in the Women's Interagency HIV Study. Diffusing capacity (DL(CO)) was significantly lower in HIV+ women (65.5% predicted vs. 72.7% predicted, P = 0.01), and self-reported dyspnea in HIV+ participants was associated with both DL(CO) impairment and airflow obstruction. Providers should be aware that DL(CO) impairment is common in HIV infection, and that either DL(CO) impairment or airflow obstruction may cause respiratory symptoms in this population.