Asthma diagnosis and airway bronchodilator response in HIV-infected patients

Gingo, Matthew R.; Wenzel, Sally E.; Steele, Chad; Kessinger, Cathy; Lucht, Lorrie; Lawther, Tammi; Busch, Michelle; Hillenbrand, Maria E.; Weinman, Renee; Slivka, William A.; McMahon, Deborah; Zhang, Yingze; Sciurba, Frank C.; Morris, Alison

doi:10.1016/j.jaci.2011.11.015

Cited by 61 publications

(68 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Researchers in one study found an association between HIV-positive patients with prior pneumonia with either PC or a bacterial pathogen and doctor-diagnosed asthma (56). A second study of HIVpositive individuals demonstrated that history of PC was associated with an obstructed spirometric pattern in lung function testing (57).…”

Section: Discussionmentioning

confidence: 99%

A Novel CD4⁺ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

Eddens

Campfield

Serody

et al. 2016

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Infection with Pneumocystis, an opportunistic fungal pathogen, can result in fulminant pneumonia in the clinical setting of patients with immunosuppression. In murine models, Pneumocystis has previously been shown to induce a CD4 1 T cell-dependent eosinophilic response in the lung capable of providing protection.Objectives: We sought to explore the role of Pneumocystis in generating asthma-like lung pathology, given the natural eosinophilic response to infection.Methods: Pneumocystis infection or antigen treatment was used to induce asthma-like pathology in wild-type mice. The roles of CD4 1 T cells and eosinophils were examined using antibody depletion and knockout mice, respectively. The presence of anti-Pneumocystis antibodies in human serum samples was detected by ELISA and Western blotting.Measurements and Main Results: Pneumocystis infection generates a strong type II response in the lung that requires CD4 1 T cells. Pneumocystis infection was capable of priming a Th2 response similar to that of a commonly studied airway allergen, the house dust mite. Pneumocystis antigen treatment was also capable of inducing allergic inflammation in the lung, resulting in anti-Pneumocystis IgE production, goblet cell hyperplasia, and increased airway resistance. In the human population, patients with severe asthma had increased levels of anti-Pneumocystis IgG and IgE compared with healthy control subjects. Patients with severe asthma with elevated antiPneumocystis IgG levels had worsened symptom scores and lung parameters such as decreased forced expiratory volume and increased residual volume compared with patients with severe asthma who had low anti-Pneumocystis IgG.Conclusions: The present study demonstrates for the first time, to our knowledge, that Pneumocystis is an airway allergen capable of inducing asthma-like lung pathology.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel CD4⁺ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

Eddens

Campfield

Serody

et al. 2016

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…First, eosinophilia in the bronchoalveolar lavage fluid of HIV-positive patients with Pneumocystis pneumonia has been well documented; however, whether a correlation exists between high eosinophil counts and lower Pneumocystis burden in these patients is unknown (32, 33). Secondly, patients with a history of Pneumocystis or bacterial pneumonia had a significantly higher rate of physician-diagnosed asthma, a disease that has a well-established eosinophilic component in regards to pathogenesis (34). Murine models of Pneumocystis have also shown STAT6, a transcription factor required for Th2 responses, is necessary for the development of airway hyperresponsiveness early in the course of infection (23).…”

Section: Discussionmentioning

confidence: 99%

Eosinophils Contribute to Early Clearance of Pneumocystis murina Infection

Eddens

Elsegeiny

Nelson

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4+ T-cell counts in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV infected individuals taking immunosuppressive drug regimens targeting T-cell activation are also susceptible. Given the crucial role of CD4+ T-cells in host defense against Pneumocystis, we used RNA-sequencing of whole lung early in infection in wild type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild type mice, a strong eosinophil signature was observed at day 14 post-Pneumocystis challenge and eosinophils were increased in the bronchoalveolar lavage fluid of wild type mice. Furthermore, eosinophilopoiesis-deficient Gata1tm6Sho/J mice were more susceptible to Pneumocystis infection when compared to BALB/c controls and bone marrow derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1−/− mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. pIL5 treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden compared to mice treated with control plasmid. Additionally, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57Bl/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1tm6Sho/J mice. Taken together, these results demonstrate that an early role of CD4+ T-cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development for Pneumocystis pneumonia in the immunosuppressed population.

show abstract

“…In contrast, the majority of asthma diagnoses in the general population occurs in children (50). Doctor-diagnosed asthma was associated with female sex, obesity, not being on cART during the study period, and a history of bacterial or Pneumocystis pneumonia (47). In addition, approximately 10% of the cohort had high sputum eosinophil counts, and there was an association between doctor-diagnosed asthma or bronchodilator response and high sputum eosinophil counts, but the majority of participants with doctor-diagnosed asthma or bronchodilator response did not have elevated sputum eosinophils, suggesting that there may be non-T helper type 2-related mechanisms causing asthma in HIV.…”

Section: Obstructive Lung Disease: Associations With Hivmentioning

confidence: 87%

“…In the Veterans Aging Cohort Study, a predominantly smoking older male cohort, asthma diagnosis was similar between individuals with and those without HIV (41). Two recent studies with a broader population of individuals with HIV have found that 11 and 21%, respectively, have an asthma diagnosis by history (doctor-diagnosed asthma) (46,47). These prevalence estimates may be greater than the estimated prevalence of approximately 7.6% in the general population (48).…”

Section: Obstructive Lung Disease: Associations With Hivmentioning

confidence: 99%

“…The causes of these apparent increases in asthma and airway disease remain unclear, but recent studies have examined characteristics of asthma in HIV. In the Pittsburgh HIV Lung cohort, 55% of participants with doctordiagnosed asthma reported onset of asthma in adulthood, often after diagnosis of HIV (47). In contrast, the majority of asthma diagnoses in the general population occurs in children (50).…”

Section: Obstructive Lung Disease: Associations With Hivmentioning

confidence: 99%

See 1 more Smart Citation

Infections in “Noninfectious” Lung Diseases

et al. 2014

Self Cite

View full text Add to dashboard Cite

Many chronic pulmonary diseases, including those that are not primarily infectious in etiology, have some aspects of their pathogenesis that are influenced by infectious organisms. Microorganisms may contribute to chronic lung diseases, either directly (i.e., overt infection) or indirectly, via the amplification of inflammatory pathways that are critical to host defense. As techniques for detecting and characterizing microorganisms have advanced, investigations of both infecting and colonizing organisms have yielded new insights into mechanisms of pulmonary disease. In addition, changes in patterns of infection and microbial resistance have important implications for treatment. Examples of these infectious-pulmonary associations, including Haemophilus influenzae infection and chronic obstructive pulmonary disease, nontuberculous mycobacteria and bronchiectasis, and human immunodeficiency virus and obstructive lung disease, are reviewed.

show abstract

Asthma diagnosis and airway bronchodilator response in HIV-infected patients

Cited by 61 publications

References 51 publications

A Novel CD4⁺ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

A Novel CD4⁺ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

Eosinophils Contribute to Early Clearance of Pneumocystis murina Infection

Infections in “Noninfectious” Lung Diseases

Contact Info

Product

Resources

About

Asthma diagnosis and airway bronchodilator response in HIV-infected patients

Cited by 61 publications

References 51 publications

A Novel CD4+ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

A Novel CD4+ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

Eosinophils Contribute to Early Clearance of Pneumocystis murina Infection

Infections in “Noninfectious” Lung Diseases

Contact Info

Product

Resources

About

A Novel CD4⁺ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

A Novel CD4⁺ T Cell–Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology