Common Cold Viruses Early After Hsct Are Associated With Life Threatening Alloimmune Lung Syndromes
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Abstract:
In lung transplantation, early infection (<100 d) with a common respiratory virus (RV) is associated with acute or chronic rejection, presenting as Bronchiolitis Obliterans (BO). After hematopoietic stem cell transplantation (HSCT) alloimmune lung syndromes (allo-LS), including Idiopathic Pneumonia Syndrome (IPS; acute) and BO (chronic), also occur, but the role of RV is unclear. In this prospective cohort study we analyzed the influence of common RV early (< 100 days) after HSCT, on the development of allo-LS and survival. 110 paediatric patients with a median age of 5 years (2 mths – 21years), were included. They received a transplant (56 matched, 54 mismatched; 33 cord blood, 77 bone marrow; 33 family, 77 unrelated) for malignant (56) and non-malignant (54) disease, after a TBI (33) or chemotherapy based (77) conditioning regimen. In 50% of patients a RV infection occurred, at a median of day +16 (range -7 to 100). RV was proven by qPCR on nasopharyngeal aspirate: Rhinovirus was found most frequent (28), followed by Parainfluenzavirus1-3, Coronavirus, Influenza A virus and Adenovirus. Clinical symptoms were mild, and all patients recovered spontaneously, despite the fact that the RV remained present for months in all patients. After a period without symptoms of at least 2 weeks, new respiratory symptoms occurred in about 50% of the RV positive patients. Based on additional examinations including negative cultures (other than RV), radiology and pulmonary function tests, 30 patients (27.2%) were diagnosed with allo-LS: 18 IPS (16.4%) and 12 BO (10.9%), after a median time of 8 weeks (2-26). Multivariable analysis showed that RV infection is an important predictor for allo-LS (p<0.0001). There was no difference between Rhinovirus versus all others. Acute Graft-versus-Host Disease (aGVHD), occurring at a median of 4 weeks (2-15), had a protective effect on the development of allo-LS (p=0.004), most likely due to higher and prolonged immunesuppression in these patients. Overall survival was 73%; in the allo-LS group this was only 53%. In multivariable analysis allo-LS was the only predictor for mortality (p= 0.04). In conclusion, early presence of RV is a predictor for the development of allo-LS. We hypothesise that infection with a common cold virus makes the lung a target for alloimmunity, leading to life threatening lung disease. Paradoxically, prolonged immune suppression, despite the local viral infection, protected against the development of allo-LS.Keywords:
Rhinovirus
Human rhinoviruses (HRV) cause respiratory infections and are associated with asthma development. We assessed HRV prevalence, types and association with respiratory symptoms in the first year of life in 20 unselected infants. HRV was detected in 32% of 825 weekly nasal swabs. Seventy-four different types of all three species were identified. HRV presence and related respiratory symptoms are highly heterogeneous.
Rhinovirus
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Bronchiolitis obliterans syndrome is the main limitation for long-term survival after lung transplantation. Some specific B cell populations are associated with long-term graft acceptance. We aimed to monitor the B cell profile during early development of bronchiolitis obliterans syndrome after lung transplantation. The B cell longitudinal profile was analyzed in peripheral blood mononuclear cells from patients with bronchiolitis obliterans syndrome and patients who remained stable over 3 years of follow-up. CD24hi CD38hi transitional B cells were increased in stable patients only, and reached a peak 24 months after transplantation, whereas they remained unchanged in patients who developed a bronchiolitis obliterans syndrome. These CD24hi CD38hi transitional B cells specifically secrete IL-10 and express CD9. Thus, patients with a total CD9+ B cell frequency below 6.6% displayed significantly higher incidence of bronchiolitis obliterans syndrome (AUC = 0.836, PPV = 0.75, NPV = 1). These data are the first to associate IL-10-secreting CD24hi CD38hi transitional B cells expressing CD9 with better allograft outcome in lung transplant recipients. CD9-expressing B cells appear as a contributor to a favorable environment essential for the maintenance of long-term stable graft function and as a new predictive biomarker of bronchiolitis obliterans syndrome-free survival.
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Rhinovirus
Common cold
Infectivity
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Rhinovirus
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Rhinovirus
Respiratory illness
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Respiratory syncytial virus(RSV) and human rhinovirus(HRV) are the most common pathogenscausing lower respiratory infectionsin young children throughout the world, which often lead to development of bronchiolitis and asthma.It is known that respiratory microbiota plays an important role in respiratory health and diseases and its interaction with RSV or HRV can affect susceptibility to and outcome of respiratory infections in young children.In this review, we summarize accumulating data of effects of RSV and HRV infections on respiratory microbiota, impact of respiratory microbiota on development of host immune system and susceptibility to and severity of these viral infections.Role of certain probiotics and commensal bacteria in potential prevention and treatment of RSV and HRV infections is also discussed.
Key words:
Respiratory Syncytial Virus; Child; Rhinovirus; Respiratory tract infections; Respiratory microbiota
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Respiratory tract
Common cold
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