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Biomedical subjects

Jan-Bas Prins

Publications and source records attributed to Jan-Bas Prins.

2 recordsLinked to original sources

Asthma remission: does it exist?

Subjects believed to have grown out of asthma often develop symptoms again later in life. Ongoing airway inflammation may determine the risk of relapse, although the mechanisms involved are still misunderstood. Additionally, patients with asthma during childhood may develop irreversible airflow obstruction ( airway remodeling) as a result of chronic airway inflammation. Recently, airway inflammation and remodeling could be demonstrated in bronchial biopsy specimens from young adults who considered themselves grown out of asthma. It is also shown that evidence of airway inflammation and remodeling can be obtained noninvasively, thereby providing the opportunity to monitor disease activity. If chronic airway inflammation and/or remodeling are consistent findings in asymptomatic subjects with a history of atopic asthma, the question arises whether natural history can be positively altered with prolonged antiinflammatory therapy. Benefits of long-term prognosis are, however, not yet shown. Since epidemiologic work has demonstrated that a certain percentage of subjects with apparently outgrown atopic asthma remains asymptomatic without needing therapy for the rest of their lives, it can be argued that "asthma remission does exist." The question is whether this percentage can be increased with prolonged antiinflammatory therapy and regular control.

Adolescent↗

Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31(hi)Ly-6C(neg) bone marrow precursors in a mouse model of asthma.

Airway dendritic cells (DCs) are held responsible for inducing sensitization to inhaled antigen, leading to eosinophilic airway inflammation, typical of asthma. However, less information is available about the role of these cells in ongoing inflammation. In a mouse model of asthma, sensitization to ovalbumin (OVA) was induced by intratracheal injection of myeloid OVA-pulsed DCs. Upon OVA aerosol challenge and induction of eosinophilic airway inflammation in sensitized mice, there was a time-dependent and almost 100-fold increase in the number of MHCII(+) CD11b(+) CD11c(+) endogenous airway DCs as well as CD11b(+) blood DCs. The mechanism of this increase was studied. Adoptive transfer experiments demonstrated that accumulation of airway DCs was not due to reduced migration to the mediastinal lymph nodes. Rather, the massive increase in airway and lymph node DCs was supported by an almost 3-fold expansion of myeloid CD31(hi)Ly-6C(neg) hematopoietic precursor cells in the bone marrow (BM). There was no change in any of the other 5 populations revealed by CD31/Ly-6C staining. When these CD31(hi)Ly-6C(neg) BM precursors were sorted and grown in granulocyte macrophage-colony-stimulating factor, they differentiated into MHCII(+) CD11c(+) DCs. The same CD31(hi)Ly-6C(neg) precursors also expressed the eotaxin receptor CCR3 and differentiated into eosinophils when grown in interleukin 5. Serum levels of eotaxin were doubled in mice with inflammation. These findings in an animal model of asthma suggest that the BM increases its output of myeloid precursors to meet the enhanced demand for DCs and eosinophils in inflamed airways.

Allergens↗