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Unlabelled: Our aim was to determine whether viral lower respiratory tract infections (LRTIs) adversely affect prematurely born infants' lung function at follow up. Seventy infants, median gestational age 34 (range, 24-35) weeks were prospectively followed; 32 had an RSV (n = 14) or another respiratory viral (n = 18) LRTI (viral LRTI group) and 38 had no LRTI (no LRTI group). Six of the viral LRTI and five of the no LRTI group had been hospitalised. Nasopharyngeal aspirates (NPAs) obtained whenever the infants had an LRTI. Lung function (functional residual capacity [FRCHe], compliance [Crs] and resistance [Rrs] of the respiratory system) was measured at 36 weeks postmenstrual age (PMA) and 1 year corrected. At 1 year, lung volume (FRCpleth) and airways resistance (Raw) were also assessed. There were no significant differences in the lung function of the two groups at 36 weeks PMA but at 1 year, the viral LRTI compared to the no LRTI group had a higher mean Raw (23 versus 17 cm H2O/l/s, p = 0.0068), the differences remained significant after adjustment., Conclusion: These results suggest viral LRTIs, regardless of whether hospitalisation is required, adversely affect prematurely born infants' airway resistance at follow up.

Unlabelled: Human rhinoviruses (HRVs) are a common cause of lower respiratory tract infections (LRTIs) and are associated with chronic respiratory morbidity. Our aim was to determine whether HRV species A or C were associated with chronic respiratory morbidity and increased health care utilisation in prematurely born infants. A number of 153 infants with a median gestational age of 34 (range 23-35) weeks were prospectively followed. Nasopharyngeal aspirates were collected whenever the infants had LRTIs regardless of hospitalisation status. Parents completed a respiratory diary card and health questionnaire about their infant when they were 11 and 12 months corrected age, respectively. The health-related cost of care during infancy was calculated from the medical records using the National Health Service (NHS) reference costing scheme and the British National Formulary for children. There were 32 infants that developed 40 HRV LRTIs; samples were available from 23 of the 32 infants for subtyping. Nine infants had HRV-A LRTIs, 13 HRV-C LRTIs, and one infant had a HRV-B LRTI. Exclusion of infants who also had RSV LRTIs revealed that the infants who had a HRV-C LRTI were more likely to wheeze (p < 0.0005) and use respiratory medications (p < 0.0005) and had more days of wheeze (p = 0.01) and used an inhaler (p = 0.02) than the no LRTI group. In addition, the respiratory cost of care was greater for the HRV-C LRTI than the no LRTI group (p < 0.0005)., Conclusion: Our results suggest HRV-C is associated with chronic respiratory morbidity during infancy in prematurely born infants.

Unlabelled: The aim of this study was to assess whether prematurely born infants have a genetic predisposition to respiratory syncytial virus (RSV) infection-related respiratory morbidity. One hundred and forty-six infants born at less than 36 weeks of gestation were prospectively followed. Nasopharygeal aspirates were obtained on every occasion the infants had a lower respiratory tract infection (LRTI) regardless of need for admission. DNA was tested for 11 single-nucleotide polymorphisms (SNPs). Chronic respiratory morbidity was assessed using respiratory health-related questionnaires, parent-completed diary cards at a corrected age of 1 year and review of hospital notes. Lung function was measured at a post menstrual age (PMA) of 36 weeks and corrected age of 1 year. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36-week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (interleukin 10 (IL10), nitric oxide synthase 2A (NOS2A), surfactant protein C (SFTPC), matrix metalloproteinase 16 (MMP16) and vitamin D receptor (VDR)) and reduced lung function at 1 year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs., Conclusions: Our results suggest that prematurely born infants may have a genetic predisposition to RSV LRTIs and subsequent respiratory morbidity which is independent of premorbid lung function.

Our aim was to determine whether rhinovirus (RV) lower respiratory tract infections (LRTIs) in prematurely born infants increase health-related cost of care during infancy. 153 infants born at <36 weeks of gestation were prospectively followed to 1 year. Cost of care was calculated from the National Health Service reference costing scheme and healthcare utilisation determined by examining hospital/general practitioner records. 20 infants developed RV LRTIs (RV group), 17 respiratory syncytial virus (RSV) LRTIs (RSV group), 12 both RV and RSV LRTIs (RV/RSV group) and 74 had no LRTI (no LRTI group). Compared with the no LRTI group, the RV/RSV LRTI group had the greatest increase in adjusted mean cost (difference GBP 5769), followed by the RV LRTI group (difference GBP 278) and, finally, the RSV LRTI group (difference GBP 172) (p=0.045). The RV group had more outpatient (p<0.05) and respiratory-related general practitioner (p<0.05) attendances, more wheezed at follow-up (p<0.001) than the no LRTI group and more had respiratory-related outpatient attendances than the RSV LRTI group (p<0.05). We conclude that RV LRTIs were associated with increased health-related cost of care during infancy; our results suggest that the RV group compared with the RSV group suffered greater chronic respiratory morbidity.

Real-time PCR is a significant improvement over viral isolation and immunofluorescence for routinely detecting respiratory viruses. We developed three real-time internally controlled multiplex RT-PCR assays for detecting nine respiratory viruses. An internal control transcript consisting of a chimeric plasmid was synthesised and incorporated into each multiplex to monitor amplification efficiency, including inhibition. Each multiplex assay was developed on the Rotor-Gene 3000 and evaluated using RNA extracts from 126 nasopharyngeal aspirates from 112 pre-term infants. All 44/126 (35%) samples positive by immunofluorescence were confirmed by multiplex RT-PCR. Additionally, respiratory syncytial virus RNA was detected in 5 samples, influenza A virus RNA in 2 samples and thirteen (10%) dual infections by multiplex RT-PCR were noted. Inclusion of the RNA internal control did not affect the amplification efficiency of the target sequences and only 2 of 1256 (0.2%) samples tested over a 12 month period were inhibitory. Together with the improved sensitivity of the internally controlled multiplex RT-PCR assays over the older technology and the ability to detect co-infections, the internal control monitored the efficiency of both the RT and PCR steps and indicated inhibition, saving time and costs on running duplicate samples with a "spiked" inhibition control., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Prematurely born infants who develop respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) have lung function abnormalities at follow-up. The aim of this study was to determine whether prematurely born infants who developed symptomatic RSV, or other viral LRTI(s), had poorer premorbid lung function than infants who did not develop LRTIs during the RSV season., Methods: Lung function (functional residual capacity (FRC), compliance (Crs) and resistance (Rrs) of the respiratory system) was measured at 36 weeks postmenstrual age. After neonatal unit discharge, nasopharyngeal aspirates were obtained whenever the infants had an LRTI, regardless of whether this was in the community or in hospital. Nasopharyngeal aspirates were examined for RSV A and B, rhinovirus, influenza A and B, parainfluenza 1, 2 and 3, human metapneumovirus and adenovirus., Results: 159 infants with a median gestational age of 34 (range 23-36) weeks were prospectively followed. 73 infants developed LRTIs: 27 had at least one RSV LRTI and 31 had at least one other viral LRTI, but not an RSV LRTI. Overall, there were no significant differences in the FRC (p=0.54), Crs (p=0.11) or Rrs (p=0.12) results between those who developed an RSV or other viral LRTI and those who did not develop an LRTI. Infants with RSV or other viral LRTIs who were admitted to hospital compared with those who were not had higher Rrs results (p=0.033 and p=0.039, respectively)., Conclusion: Diminished premorbid lung function may predispose prematurely born infants to severe viral LRTIs in infancy.

Background: Chronic respiratory morbidity has been reported in prematurely born infants after respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) lower respiratory tract infections (LRTIs). The aim of this study was to determine the impact of viral LRTI on lung function at follow-up of prematurely born infants., Methods: Fifty-nine infants born before 32 weeks of gestational age were prospectively followed after neonatal unit discharge. Nasopharyngeal aspirates were obtained when the infants developed LRTIs in hospital or the community. RSV was identified by immunofluorescence and/or culture. In addition, RSV and other viral infections were identified by real time reverse transcription polymerase chain reaction. At a corrected age of 1 year, measurements of lung volume [functional residual capacity (FRC)pleth] and airway resistance (R(aw)) were made by plethysmography, and lung volume was also assessed by helium gas dilution (FRC(He)). Before the measurements, parents completed diary cards for 1 month documenting on a daily basis whether their infant wheezed, coughed, or required bronchodilator therapy., Results: Twenty-five infants had at least 1 proven RSV LRTI (RSV-positive group). The RSV-positive group compared with the rest of the cohort had similar lung volumes, but significantly higher R(aw) (P = 0.002), more days of wheeze (P < 0.001), and bronchodilator requirement (P = 0.027). Regression analysis also identified that hMPV LRTI was associated with elevated airways resistance at follow-up., Conclusion: RSV and hMPV LRTIs in prematurely born infants are associated with abnormal lung function at follow-up.

Background: Diminished lung function appears to be a risk factor for respiratory syncytial virus (RSV) infection/bronchiolitis in term born infants., Aims: To determine if diminished lung function prior to neonatal unit discharge was associated with subsequent symptomatic RSV lower respiratory tract infection (LRTI) and respiratory morbidity in prematurely born infants., Methods: Of 39 infants in a tertiary neonatal intensive care unit (median gestational age 28 weeks, range 23-31), 20 had bronchopulmonary dysplasia. Lung function (compliance and resistance of the respiratory system (C(rs) and R(rs)) and functional residual capacity (FRC)) was measured on the neonatal unit at 36 weeks postmenstrual age (PMA). Following neonatal unit discharge, nasopharyngeal aspirates were obtained on every occasion, at home or in hospital, an infant had an LRTI. RSV was identified by immunofluorescence and/or culture., Results: The 15 infants who suffered a symptomatic RSV LRTI had a higher mean R(rs) and suffered more wheeze at follow up than the rest of the cohort. Regression analysis showed that a high R(rs) was significantly associated with a symptomatic RSV LRTI; significant factors for cough were a high R(rs) and a symptomatic RSV LRTI, and for wheeze were a high R(rs)., Conclusion: Prematurely born infants, who had a symptomatic RSV LRTI and/or respiratory morbidity at follow up, had worse lung function prior to neonatal unit discharge.

Background: A study was undertaken to determine the impact of respiratory syncytial virus (RSV) infection, both in hospital and the community, on healthcare utilisation and respiratory morbidity in prematurely born infants and to identify risk factors for symptomatic RSV infection., Methods: A hospital and community follow up study was undertaken of 126 infants born before 32 weeks of gestational age. Healthcare utilisation (hospital admissions and general practitioner attendances) in the first year, respiratory morbidity at follow up (wheeze and cough documented by parent completed diary cards), and RSV positive lower respiratory tract infections (LRTIs) were documented. Nasopharyngeal aspirates were obtained for immunofluorescence and culture for RSV whenever the infants had an LRTI, either in the community or in hospital., Results: Forty two infants had an RSV positive LRTI (RSV group), 50 had an RSV negative LRTI (RSV negative LRTI group), and 32 infants had no LRTI (no LRTI group). Compared with the RSV negative LRTI and the no LRTI groups, the RSV group required more admissions (p=0.392, p<0.001) and days in hospital (p=0.049, p=0.006) and had more cough (p=0.05, p=0.038) and wheeze (p=0.003, p=0.003) at follow up. Significant risk factors for symptomatic RSV LRTI were number of siblings (p=0.035) and maternal smoking in pregnancy (p=0.005), for cough were number of siblings (p=0.002) and RSV LRTI (p=0.02), and for wheeze was RSV LRTI (p=0.019)., Conclusion: RSV infection, even if hospital admission is not required, is associated with increased subsequent respiratory morbidity in prematurely born infants.