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.
Abstract Background Fatigue is a commonly reported clinical symptom, yet research on fatigue in children with severe asthma is missing. We aimed to explore the extent of fatigue in severe pediatric asthma and identify associated factors. Method This study was conducted within the Pediatric Asthma Non‐Invasive Diagnostic Approaches (PANDA), an observational cohort of 6‐ to 17‐year‐old Dutch children with severe asthma. The Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL™‐MFS) was used to measure self‐reported fatigue. Fatigue levels were compared with a general pediatric Dutch population using linear regression, and quantifying the prevalence of “fatigued” (−2 < Standard deviations [SD] ≤ −1) and “severely fatigued” (SD ≤ −2) children. Secondly, we performed linear regression analyses to explore whether fatigue levels were independently associated with asthma attacks, comorbidities, medication, pulmonary function, symptom control, and asthma‐related quality of life (QoL). Results Severe pediatric asthma patients ( n = 78, mean age 11.8 ± 3.1 years) reported significantly more fatigue than Dutch peers ( n = 328, mean age 11.8 ± 3.2 years) mean difference in z ‐score: −0.68; 95%CI −0.96, −0.40. In the severe asthma group, 28.2% scored as “fatigued” and 15.4% as “severely fatigued,” compared with 14.0% and 3.4% in the general population. In pediatric asthma patients, asthma‐related QoL ( β = 0.77, p < .01, Δ R 2 = .43), symptom control ( β = 0.56, p < .01, Δ R 2 = .24) and a dysfunctional breathing pattern ( β = −0.36, p < .01, Δ R 2 = .12) were most strongly associated with fatigue scores. Conclusion Fatigue is a common symptom in children with severe asthma and is associated with multiple clinical factors and patient‐reported outcomes. It should be considered as an important treatment target.
Abstract A longitudinal study in 2004 and 2005 detected polyomaviruses WU and KI in 44% and 17% of children with and without respiratory symptoms, respectively, in the Netherlands. In some children both viruses were detected for long periods. In several symptomatic children no other respiratory pathogen was detected.
Dutch guidelines recommend to consider intravenous magnesium sulfate (iv MgSO4) as a treatment option in case of failure of first line treatment in both children with exacerbations of acute episodic viral wheeze (AEVW) and acute asthma (AA). The implications on the actual use of iv MgSO4 iv in daily practice in both groups are unknown. Therefore, we conducted a cross-sectional nationwide survey to evaluate the use of iv MgSO4 in children with AEVW and AA.A questionnaire was handed out to pediatricians and pediatric residents in one academic and six community teaching hospitals.In 111 respondents, 76% reported regular use of iv MgSO4 in children with AEVW and 96% in children with AA. In total 89% and 93% of users were convinced iv MgSO4 was effective in children with AEVW and AA, respectively. Adverse effects, mainly hypotension, were identified by 23% and 17% of users in AEVW and AA, respectively. Most common reasons not to give MgSO4 were lack of evidence and small amount of studies.IV MgSO4 is reported to be widely used in Dutch practice in both young children with AEVW and older children with AA by respondents, while the national guidelines advise only to consider this treatment option.
Human rhinoviruses (HRVs) are an important cause of respiratory tract infections.We questioned whether the high prevalence rates of HRVs found in epidemiological studies is due to long-term individual continuity or a result of frequent infections with different HRV subtypes.In a 6-month winter period 18 healthy controls, aged 0-7 years, were at least sampled every two weeks for HRV-PCR, irrespective of respiratory symptoms. All HRV positive samples were genotyped to determine HRV diversity.In total 272 samples were collected. HRV was found in 101/272 (37%) samples. Genotyping revealed 27 different HRV subtypes. A median of 3.0 different HRV subtypes was found per child. Re-infections and continuity with identical HRV sequences were observed. The number of HRVs were higher in the youngest age group (p=0.01) and they had more different HRV subtypes (p=0.05) compared to oldest age group.We found a high HRV exposition with a considerable diverse population of HRV subtypes in young children. These results have major implications for future research into the pathogenic role of HRV in respiratory diseases. Characterisation of subtypes will be necessary to discriminate between prolonged continuity and re-infections in patients with respiratory diseases.
