Weight gain during treatment for a cystic fibrosis exacerbation http://ow.ly/f1zl30dU9AO

Barr, Helen L.

Barrett, David

Cámara, Miguel

Dewar, Jane

Fogarty, Andrew W.

Forrester, Doug

Honeybourne, David

Knox, Alan

Nash, Edward

Smyth, Alan

Whitehouse, Joanna

Williams, Paul

Name not available

Weight gain during acute treatment of an initial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adults with cystic fibrosis

Helen L. Barr

Miguel Cámara

David Barrett

Paul Williams

Doug Forrester

Alan Smyth

David Honeybourne

Joanna Whitehouse

Edward Nash

Jane Dewar

Alan Knox

Andrew W. Fogarty

Crossref

ERJ Open Research

Nottingham eTheses

Barr, Helen L

Whitehouse, Joanna L

Nash, Edward F

Fogarty, Andrew W

HEFT Repository

Weight gain during acute treatment of an initial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adults with cystic fibrosis.

Nottingham ePrints

Barr, Helen L. and Cámara, Miguel and Barrett, David and Williams, Paul and Forrester, Doug and Smyth, Alan and Honeybourne, David and Whitehouse, Joanna and Nash, Edward and Dewar, Jane and Knox, Alan and Fogarty, Andrew W. (2017) Weight gain during acute treatment of an initial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adults with cystic fibrosis. ERJ Open Research, 3 (3). pp. 1-4. ISSN 2312-0541 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/45179/1/Barr%202017%20ERJ.pdfCopyright and reuse: The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions.This article is made available under the Creative Commons Attribution Non-commercial licence and may be reused according to the conditions of the licence.  For more details see: http://creativecommons.org/licenses/by-nc/2.5/A note on versions: The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher’s version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.ukWeight gain during acute treatment of aninitial pulmonary exacerbation isassociated with a longer interval to thenext exacerbation in adults with cysticfibrosisTo the Editor:Cystic fibrosis (CF) results in a variety of clinical phenotypes, including increased susceptibility topulmonary infections [1] and malnutrition [2]. As a consequence, one of the priorities in the clinical carefor individuals with a diagnosis of CF is to treat chest infections promptly [3], with the aim of minimisingthe decline in lung function that occurs in individuals who experience recurrent pulmonary exacerbations [4].Optimising nutrition is another important consideration in the care of patients with CF [3]. It is wellrecognised that nutritional status and lung function are correlated [5] and that individuals with lowerlevels of nutrition have increased mortality [6] compared to those individuals with better nutrition.Treatment of pulmonary exacerbations represents an opportunity to intervene to improve nutrition. Wehypothesised that individuals who gain more weight during treatment of a pulmonary exacerbation maysubsequently have a better clinical outcome than those who did not. We used an existing dataset to testthis hypothesis in a secondary analysis of a population of adult CF patients with known chronic infectionwith Pseudomonas aeruginosa who were treated for a pulmonary exacerbation.The study population consisted of 59 adults with CF known to have chronic pulmonary infection withP. aeruginosa, who were recruited for a biomarker study [7] and have a pulmonary exacerbation as definedby the Rosenfeld criteria [8]. The inclusion and exclusion criteria have been reported previously [7]. Boththe choice of antibiotic and the duration of treatment were chosen at the discretion of the patient’sclinician, and treatment included nutritional support from a CF specialist dietician. At the start and end oftreatment, patients were weighed. Pulmonary function tests were performed according to the jointEuropean Respiratory Society/American Thoracic Society criteria [9] at the end of the exacerbation.Patients were recruited between July 28, 2009 and December 8, 2010 and were followed up until March 1,2012. The time to next exacerbation was documented as the interval between the date of completion ofantibiotics during the initial episode and the date intravenous antibiotics were commenced for thesubsequent pulmonary exacerbation. The study was approved by the local ethics committee (NREC1: 09/H0407/1), and informed written consent was obtained for all participants.Data were analysed using Cox regression with the time to next exacerbation as the dependent variable. Thefollowing co-variates were added to the univariate model of the association between change in weight andtime to subsequent treatment for pulmonary exacerbation model to explore potential confounding factors:sex, age in categories, forced expiratory volume in one second (FEV1) at discharge, height, duration ofpulmonary P. aeruginosa infection in quintiles, long-term use of oral steroids, gastro-oesophageal refluxdisease, pancreatic insufficiency and diabetes mellitus. A confounding factor was defined as one thatchanged the hazard ratio (HR) by 10% or more. The final model was tested to ensure that the Cox@ERSpublicationsWeight gain during treatment for a cystic fibrosis exacerbation http://ow.ly/f1zl30dU9AOCite this article as: Barr HL, Cámara M, Barrett D, et al. Weight gain during acute treatment of aninitial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adultswith cystic fibrosis. ERJ Open Res 2017; 3: 00057-2017 [https://doi.org/10.1183/23120541.00057-2017].Copyright ©ERS 2017. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.https://doi.org/10.1183/23120541.00057-2017 ERJ Open Res 2017; 3: 00057-2017ORIGINAL RESEARCH LETTERregression proportional hazard assumption was not violated using Schoenfeld residuals. The analysis usedSTATA 14 statistical software (StataCorp, College Station, TX, USA).The clinical details of the 59 participants are summarised in table 1. The median duration of treatmentwith antibiotics was 14 days (interquartile range (IQR) of 14–14). The median weight gain was +1.00 kg,with an IQR of −0.10 to +2.30 kg. A total of 58 (98%) participants had a pulmonary exacerbation duringthe follow-up period, and the median interval to subsequent exacerbation was 2.8 months (IQR1.3–5.4 months). Gaining weight during treatment for a pulmonary exacerbation was associated with alonger period to the subsequent next pulmonary exacerbation after the end of antibiotic treatment. A 1 kgincrease in weight over the course of treatment was associated with an HR of 0.83 (95% CI 0.70–0.98).Addition of potential confounding factors did not modify this association, so they were not incorporatedTABLE 1 Baseline participant characteristicsMale 33 (56%)Age years 28 (17–59)GenotypeF508del homozygous 23 (39%)F508del heterozygous 19 (32%)Other 6 (10%)Unknown 11 (19%)ComorbiditiesPancreatic insufficiency 54 (92%)CF-related diabetes mellitus 32 (54%)CF-related liver disease 13 (22%)ABPA 8 (14%)Asthma 2 (3%)GORD 24 (41%)Maintenance therapiesNebulised colistin 37 (63%)Nebulised tobramycin 6 (10%)Nebulised dornase alpha 35 (59%)Nebulised hypertonic saline 20 (34%)Oral corticosteroids 10 (17%)Oral azithromycin 48 (81%)Duration of Pseudomonas aeruginosa infection years 7.7 (0.3–14.4)Baseline sputum microbiologyP. aeruginosa 52 (88%)MSSA 8 (14%)MRSA 3 (5%)Candida albicans 4 (7%)Aspergillus fumigatus 2 (3%)Haemophilus influenzae 1 (2%)No respiratory pathogens 3 (5%)Intravenous antibiotic administeredTobramycin 31 (53%)Ceftazidime 28 (47%)Colomycin 24 (41%)Meropenem 24 (41%)Aztreonam 7 (12%)Piptazobactam 5 (8%)Other 5 (8%)SpirometryFEV1# L 1.70±0.71FEV1# % predicted 47.0±17.0Anthropometric measuresHeight m 1.68±0.09BMI kg·m−2 21.9±3.7Change in weight kg +1.00 (−0.10–+2.30)Data are presented as n (%), median (range) or mean±SD. CF: cystic fibrosis; ABPA: allergicbronchopulmonary aspergillosis; GORD: gastro-oesophageal reflux disease; MSSA: methicillin-sensitiveStaphylococcus aureus; MRSA: methicillin-resistant S. aureus; BMI: body mass index. #: n=57.https://doi.org/10.1183/23120541.00057-2017 2ORIGINAL RESEARCH LETTER | H.L. BARR ET AL.into the final model. After adjustment for disease severity using FEV1, the HR decreased to 0.79 (95% CI0.67–0.94) per kg increase in weight.This is the first study to explore the association of change in weight during a pulmonary exacerbation withthe interval for subsequent pulmonary exacerbations in adults with CF. These data show that greaterweight gain is associated with a longer exacerbation-free interval, even after adjustment for pulmonarydisease severity as measured by lung function.The strengths of the study include the well-characterised cohort, which is broadly representative of patientsattending two UK adult CF specialist centres. The availability of weight data from patients at the beginningand end of their pulmonary exacerbation allowed confidence in the accuracy of these measurements. Lungfunction measurements at end of treatment permitted adjustment for disease severity, which represents animportant potential confounding factor, providing confidence that these associations are reliable. The longfollow-up period ensured that a high proportion of patients had an exacerbation during this interval. Nopatients were lost to follow-up, thus eliminating this potential cause of bias.Several limitations in our study warrant consideration. The main concern is that this analysis represents asecondary analysis of data and hence these data should be considered hypothesis-generating rather than adefinitive result. As a consequence of this, there were no data collected on nutritional interventions forindividual patients. The initiation of treatment for a pulmonary exacerbation has an encounter-basedcomponent and may therefore be based on subjective assessment by either the clinician or the patient.This can range from an unexpected emergency admission to a more planned course of treatment, withdifferences varying between individuals that are difficult to measure. There were no standardised data onbaseline weight, so acute weight loss during the acute exacerbation prior to treatment could not beassessed. As this is an observational study, we are unable to exclude residual confounding by variations inmedical care.The study of factors that prevent or delay pulmonary exacerbations is important, as these are wellrecognised to be associated with accelerated loss of lung function in adults [4, 10], decreases in quality oflife that are independent of measures of disease severity [11] and mortality [12]. The observation that again in weight while receiving treatment for a pulmonary exacerbation is associated with a longersubsequent exacerbation-free interval is an important one, as weight gain is a therapeutic outcome in itselfin the context of CF. It is not clear if this association is causal; i.e. a gain in weight protects againstsubsequent pulmonary exacerbations or is simply indicative of a good clinical response to the treatment ofthe respiratory infection that triggered the exacerbation. For example, a patient with a rapid clinicalresponse to antibiotic treatment would be expected to mobilise sooner and have a better appetite, thuspromoting more weight gain over the period of receiving treatment with i.v. antibiotics. Future studies inthis area should consider targeting weight gain as an outcome variable and assessing the impact onsubsequent disease activity, ideally in the context of a randomised clinical trial. This could represent apotential quality improvement target that could be used to compare institutional care [13, 14] and providea better clinical outcome than lung function, where a good response after treatment for pulmonaryexacerbation is not positively related with a longer time to the next exacerbation [15]. It is worthcommenting on the baseline sputum microbiology, because, although all patients were selected on thebasis of prior P. aeruginosa infection, 88% grew this microbe at entry to the study and 5% grew norespiratory pathogens at all. This correlates with clinical experience, where sputum microbiology does notalways correlate with prior results or clinical status.In summary, weight gain during treatment of a pulmonary exacerbation is associated with a longerinterval until the next pulmonary exacerbation. This represents a modifiable risk factor for pulmonaryexacerbations that has the potential to improve quality of life and clinical care in individuals with CF.Helen L. Barr1, Miguel Cámara2, David Barrett3, Paul Williams2, Doug Forrester1, Alan Smyth4,David Honeybourne5, Joanna Whitehouse5, Edward Nash5, Jane Dewar6, Alan Knox1 andAndrew W. Fogarty71Division of Respiratory Medicine, University of Nottingham, Nottingham, UK. 2Centre for BiomolecularSciences, School of Life Sciences, University of Nottingham, Nottingham, UK. 3School of Pharmacy,University of Nottingham, Nottingham, UK. 4Department of Child Health, University of Nottingham,Nottingham, UK. 5West Midlands Adult CF Centre, Heart of England NHS Foundation Trust, Birmingham,UK. 6Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham,UK. 7Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.Correspondence: Andrew W. Fogarty, Division of Epidemiology and Public Health, University ofNottingham, Medical School, Nottingham NG7 2UH, UK. E-mail: andrew.fogarty@nottingham.ac.ukhttps://doi.org/10.1183/23120541.00057-2017 3ORIGINAL RESEARCH LETTER | H.L. BARR ET AL.Received: April 26 2017 | Accepted after revision: July 03 2017Support statement: This study was supported by the UK Medical Research Council. Funding informationfor this article has been deposited with the Crossref Funder Registry.Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.comAcknowledgements: The authors would like to thank all the participants of this study for their help and support.Author contributions: A. Knox, A. Smyth, D. Forrester, A. Fogarty, D. Barrett, M. Camara conceived the study. H. Barr,J. Dewar, D. Honeybourne, J. Whitehead, and E. Nash collected the data. A. Fogarty carried out the analysis. All authorscontributed to the study and have read and approved the final manuscript.References1 Ratjen F, Doring G. Cystic fibrosis. Lancet 2003; 361: 681–689.2 Matel J. Nutritional management of cystic fibrosis. J Parenter Enteral Nutr 2012; 36: 60S–67S.3 Smyth A, Bell S, Bojcin S, et al. European Cystic Fibrosis Society standards of care: best practice guidelines.J Cystic Fibrosis 2014; 13: S23–S42.4 Sanders D, Bittner R, Rosenfeld M, et al. Pulmonary exacerbations are associated with subsequent FEV1 decline inboth adults and children with cystic fibrosis. Pediatr Pulmonol 2011; 46: 393–400.5 Forrester D, Knox A, Smyth A, et al. Are different measures of body habitus associated with lung function inindividuals with cystic fibrosis? A cross-sectional study. J Cystic Fibrosis 2013; 12: 284–289.6 Fogarty A, Britton J, Clayton A, et al. Are measures of body habitus associated with mortality in cystic fibrosis?Chest 2012; 142: 712–717.7 Barr H, Halliday N, Camara M, et al. Pseudomonas aeruginosa quorum sensing molecules correlate with clinicalstatus in cystic fibrosis. Eur Resp J 2015; 46: 1046–1054.8 Rosenfeld M, Emerson J, Williams-Warren J, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr2001; 139: 359–365.9 Miller M, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 2005; 26: 319–338.10 Amadori A, Antonelli A, Balteri I, et al. Recurrent exacerbations affect FEV1 decline in adult patients with cysticfibrosis. Respir Med 2009; 103: 407–413.11 Britto M, Kotagal U, Hornung R, et al. Impact of recent pulmonary exacerbations on quality of life in patientswith cystic fibrosis. Chest 2002; 121: 64–72.12 Mayer-Hamblett N, Rosenfeld M, Emerson J, et al. Developing cystic fibrosis lung transplant referral criteria usingpredictiors of 2-year mortality. Am J Respir Crit Care Med 2002; 166: 1550–1555.13 Schechter M, Fink A, Homa K, et al. The Cystic Fibrosis Foundation Patient Registry as a tool for use in qualityimprovement. BMJ Qual Saf 2014; 23: i9–i14.14 Godfrey M, Oliver B. Accelerating the rate of improvement in cystic fibrosis care: contributions and insights of thelearning and leadership collaborative. BMJ Qual Saf 2014; 23: i23–i32.15 Helshe S, Goss C, Thompson V, et al. Short-term and long-term response to pulmonary exacerbation in cysticfibrosis. Thorax 2016; 71: 223–229.https://doi.org/10.1183/23120541.00057-2017 4ORIGINAL RESEARCH LETTER | H.L. BARR ET AL.

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C�mara, Miguel

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Weight gain during acute treatment of aninitial pulmonary exacerbation isassociated with a longer interval to thenext exacerbation in adults with cysticfibrosisTo the Editor:Cystic fibrosis (CF) results in a variety of clinical phenotypes, including increased susceptibility topulmonary infections [1] and malnutrition [2]. As a consequence, one of the priorities in the clinical carefor individuals with a diagnosis of CF is to treat chest infections promptly [3], with the aim of minimisingthe decline in lung function that occurs in individuals who experience recurrent pulmonary exacerbations [4].Optimising nutrition is another important consideration in the care of patients with CF [3]. It is wellrecognised that nutritional status and lung function are correlated [5] and that individuals with lowerlevels of nutrition have increased mortality [6] compared to those individuals with better nutrition.Treatment of pulmonary exacerbations represents an opportunity to intervene to improve nutrition. Wehypothesised that individuals who gain more weight during treatment of a pulmonary exacerbation maysubsequently have a better clinical outcome than those who did not. We used an existing dataset to testthis hypothesis in a secondary analysis of a population of adult CF patients with known chronic infectionwith Pseudomonas aeruginosa who were treated for a pulmonary exacerbation.The study population consisted of 59 adults with CF known to have chronic pulmonary infection withP. aeruginosa, who were recruited for a biomarker study [7] and have a pulmonary exacerbation as definedby the Rosenfeld criteria [8]. The inclusion and exclusion criteria have been reported previously [7]. Boththe choice of antibiotic and the duration of treatment were chosen at the discretion of the patient’sclinician, and treatment included nutritional support from a CF specialist dietician. At the start and end oftreatment, patients were weighed. Pulmonary function tests were performed according to the jointEuropean Respiratory Society/American Thoracic Society criteria [9] at the end of the exacerbation.Patients were recruited between July 28, 2009 and December 8, 2010 and were followed up until March 1,2012. The time to next exacerbation was documented as the interval between the date of completion ofantibiotics during the initial episode and the date intravenous antibiotics were commenced for thesubsequent pulmonary exacerbation. The study was approved by the local ethics committee (NREC1: 09/H0407/1), and informed written consent was obtained for all participants.Data were analysed using Cox regression with the time to next exacerbation as the dependent variable. Thefollowing co-variates were added to the univariate model of the association between change in weight andtime to subsequent treatment for pulmonary exacerbation model to explore potential confounding factors:sex, age in categories, forced expiratory volume in one second (FEV1) at discharge, height, duration ofpulmonary P. aeruginosa infection in quintiles, long-term use of oral steroids, gastro-oesophageal refluxdisease, pancreatic insufficiency and diabetes mellitus. A confounding factor was defined as one thatchanged the hazard ratio (HR) by 10% or more. The final model was tested to ensure that the Cox@ERSpublicationsWeight gain during treatment for a cystic fibrosis exacerbation http://ow.ly/f1zl30dU9AOCite this article as: Barr HL, Cámara M, Barrett D, et al. Weight gain during acute treatment of aninitial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adultswith cystic fibrosis. ERJ Open Res 2017; 3: 00057-2017 [https://doi.org/10.1183/23120541.00057-2017].Copyright ©ERS 2017. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.https://doi.org/10.1183/23120541.00057-2017 ERJ Open Res 2017; 3: 00057-2017ORIGINAL RESEARCH LETTERregression proportional hazard assumption was not violated using Schoenfeld residuals. The analysis usedSTATA 14 statistical software (StataCorp, College Station, TX, USA).The clinical details of the 59 participants are summarised in table 1. The median duration of treatmentwith antibiotics was 14 days (interquartile range (IQR) of 14–14). The median weight gain was +1.00 kg,with an IQR of −0.10 to +2.30 kg. A total of 58 (98%) participants had a pulmonary exacerbation duringthe follow-up period, and the median interval to subsequent exacerbation was 2.8 months (IQR1.3–5.4 months). Gaining weight during treatment for a pulmonary exacerbation was associated with alonger period to the subsequent next pulmonary exacerbation after the end of antibiotic treatment. A 1 kgincrease in weight over the course of treatment was associated with an HR of 0.83 (95% CI 0.70–0.98).Addition of potential confounding factors did not modify this association, so they were not incorporatedTABLE 1 Baseline participant characteristicsMale 33 (56%)Age years 28 (17–59)GenotypeF508del homozygous 23 (39%)F508del heterozygous 19 (32%)Other 6 (10%)Unknown 11 (19%)ComorbiditiesPancreatic insufficiency 54 (92%)CF-related diabetes mellitus 32 (54%)CF-related liver disease 13 (22%)ABPA 8 (14%)Asthma 2 (3%)GORD 24 (41%)Maintenance therapiesNebulised colistin 37 (63%)Nebulised tobramycin 6 (10%)Nebulised dornase alpha 35 (59%)Nebulised hypertonic saline 20 (34%)Oral corticosteroids 10 (17%)Oral azithromycin 48 (81%)Duration of Pseudomonas aeruginosa infection years 7.7 (0.3–14.4)Baseline sputum microbiologyP. aeruginosa 52 (88%)MSSA 8 (14%)MRSA 3 (5%)Candida albicans 4 (7%)Aspergillus fumigatus 2 (3%)Haemophilus influenzae 1 (2%)No respiratory pathogens 3 (5%)Intravenous antibiotic administeredTobramycin 31 (53%)Ceftazidime 28 (47%)Colomycin 24 (41%)Meropenem 24 (41%)Aztreonam 7 (12%)Piptazobactam 5 (8%)Other 5 (8%)SpirometryFEV1# L 1.70±0.71FEV1# % predicted 47.0±17.0Anthropometric measuresHeight m 1.68±0.09BMI kg·m−2 21.9±3.7Change in weight kg +1.00 (−0.10–+2.30)Data are presented as n (%), median (range) or mean±SD. CF: cystic fibrosis; ABPA: allergicbronchopulmonary aspergillosis; GORD: gastro-oesophageal reflux disease; MSSA: methicillin-sensitiveStaphylococcus aureus; MRSA: methicillin-resistant S. aureus; BMI: body mass index. #: n=57.https://doi.org/10.1183/23120541.00057-2017 2ORIGINAL RESEARCH LETTER | H.L. BARR ET AL.into the final model. After adjustment for disease severity using FEV1, the HR decreased to 0.79 (95% CI0.67–0.94) per kg increase in weight.This is the first study to explore the association of change in weight during a pulmonary exacerbation withthe interval for subsequent pulmonary exacerbations in adults with CF. These data show that greaterweight gain is associated with a longer exacerbation-free interval, even after adjustment for pulmonarydisease severity as measured by lung function.The strengths of the study include the well-characterised cohort, which is broadly representative of patientsattending two UK adult CF specialist centres. The availability of weight data from patients at the beginningand end of their pulmonary exacerbation allowed confidence in the accuracy of these measurements. Lungfunction measurements at end of treatment permitted adjustment for disease severity, which represents animportant potential confounding factor, providing confidence that these associations are reliable. The longfollow-up period ensured that a high proportion of patients had an exacerbation during this interval. Nopatients were lost to follow-up, thus eliminating this potential cause of bias.Several limitations in our study warrant consideration. The main concern is that this analysis represents asecondary analysis of data and hence these data should be considered hypothesis-generating rather than adefinitive result. As a consequence of this, there were no data collected on nutritional interventions forindividual patients. The initiation of treatment for a pulmonary exacerbation has an encounter-basedcomponent and may therefore be based on subjective assessment by either the clinician or the patient.This can range from an unexpected emergency admission to a more planned course of treatment, withdifferences varying between individuals that are difficult to measure. There were no standardised data onbaseline weight, so acute weight loss during the acute exacerbation prior to treatment could not beassessed. As this is an observational study, we are unable to exclude residual confounding by variations inmedical care.The study of factors that prevent or delay pulmonary exacerbations is important, as these are wellrecognised to be associated with accelerated loss of lung function in adults [4, 10], decreases in quality oflife that are independent of measures of disease severity [11] and mortality [12]. The observation that again in weight while receiving treatment for a pulmonary exacerbation is associated with a longersubsequent exacerbation-free interval is an important one, as weight gain is a therapeutic outcome in itselfin the context of CF. It is not clear if this association is causal; i.e. a gain in weight protects againstsubsequent pulmonary exacerbations or is simply indicative of a good clinical response to the treatment ofthe respiratory infection that triggered the exacerbation. For example, a patient with a rapid clinicalresponse to antibiotic treatment would be expected to mobilise sooner and have a better appetite, thuspromoting more weight gain over the period of receiving treatment with i.v. antibiotics. Future studies inthis area should consider targeting weight gain as an outcome variable and assessing the impact onsubsequent disease activity, ideally in the context of a randomised clinical trial. This could represent apotential quality improvement target that could be used to compare institutional care [13, 14] and providea better clinical outcome than lung function, where a good response after treatment for pulmonaryexacerbation is not positively related with a longer time to the next exacerbation [15]. It is worthcommenting on the baseline sputum microbiology, because, although all patients were selected on thebasis of prior P. aeruginosa infection, 88% grew this microbe at entry to the study and 5% grew norespiratory pathogens at all. This correlates with clinical experience, where sputum microbiology does notalways correlate with prior results or clinical status.In summary, weight gain during treatment of a pulmonary exacerbation is associated with a longerinterval until the next pulmonary exacerbation. This represents a modifiable risk factor for pulmonaryexacerbations that has the potential to improve quality of life and clinical care in individuals with CF.Helen L. Barr1, Miguel Cámara2, David Barrett3, Paul Williams2, Doug Forrester1, Alan Smyth4,David Honeybourne5, Joanna Whitehouse5, Edward Nash5, Jane Dewar6, Alan Knox1 andAndrew W. Fogarty71Division of Respiratory Medicine, University of Nottingham, Nottingham, UK. 2Centre for BiomolecularSciences, School of Life Sciences, University of Nottingham, Nottingham, UK. 3School of Pharmacy,University of Nottingham, Nottingham, UK. 4Department of Child Health, University of Nottingham,Nottingham, UK. 5West Midlands Adult CF Centre, Heart of England NHS Foundation Trust, Birmingham,UK. 6Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham,UK. 7Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.Correspondence: Andrew W. Fogarty, Division of Epidemiology and Public Health, University ofNottingham, Medical School, Nottingham NG7 2UH, UK. E-mail: andrew.fogarty@nottingham.ac.ukhttps://doi.org/10.1183/23120541.00057-2017 3ORIGINAL RESEARCH LETTER | H.L. BARR ET AL.Received: April 26 2017 | Accepted after revision: July 03 2017Support statement: This study was supported by the UK Medical Research Council. Funding informationfor this article has been deposited with the Crossref Funder Registry.Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.comAcknowledgements: The authors would like to thank all the participants of this study for their help and support.Author contributions: A. Knox, A. Smyth, D. Forrester, A. Fogarty, D. Barrett, M. Camara conceived the study. H. Barr,J. Dewar, D. Honeybourne, J. Whitehead, and E. Nash collected the data. A. Fogarty carried out the analysis. All authorscontributed to the study and have read and approved the final manuscript.References1 Ratjen F, Doring G. Cystic fibrosis. Lancet 2003; 361: 681–689.2 Matel J. Nutritional management of cystic fibrosis. J Parenter Enteral Nutr 2012; 36: 60S–67S.3 Smyth A, Bell S, Bojcin S, et al. European Cystic Fibrosis Society standards of care: best practice guidelines.J Cystic Fibrosis 2014; 13: S23–S42.4 Sanders D, Bittner R, Rosenfeld M, et al. Pulmonary exacerbations are associated with subsequent FEV1 decline inboth adults and children with cystic fibrosis. Pediatr Pulmonol 2011; 46: 393–400.5 Forrester D, Knox A, Smyth A, et al. Are different measures of body habitus associated with lung function inindividuals with cystic fibrosis? A cross-sectional study. J Cystic Fibrosis 2013; 12: 284–289.6 Fogarty A, Britton J, Clayton A, et al. Are measures of body habitus associated with mortality in cystic fibrosis?Chest 2012; 142: 712–717.7 Barr H, Halliday N, Camara M, et al. Pseudomonas aeruginosa quorum sensing molecules correlate with clinicalstatus in cystic fibrosis. Eur Resp J 2015; 46: 1046–1054.8 Rosenfeld M, Emerson J, Williams-Warren J, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr2001; 139: 359–365.9 Miller M, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 2005; 26: 319–338.10 Amadori A, Antonelli A, Balteri I, et al. Recurrent exacerbations affect FEV1 decline in adult patients with cysticfibrosis. Respir Med 2009; 103: 407–413.11 Britto M, Kotagal U, Hornung R, et al. Impact of recent pulmonary exacerbations on quality of life in patientswith cystic fibrosis. Chest 2002; 121: 64–72.12 Mayer-Hamblett N, Rosenfeld M, Emerson J, et al. Developing cystic fibrosis lung transplant referral criteria usingpredictiors of 2-year mortality. Am J Respir Crit Care Med 2002; 166: 1550–1555.13 Schechter M, Fink A, Homa K, et al. The Cystic Fibrosis Foundation Patient Registry as a tool for use in qualityimprovement. BMJ Qual Saf 2014; 23: i9–i14.14 Godfrey M, Oliver B. Accelerating the rate of improvement in cystic fibrosis care: contributions and insights of thelearning and leadership collaborative. BMJ Qual Saf 2014; 23: i23–i32.15 Helshe S, Goss C, Thompson V, et al. Short-term and long-term response to pulmonary exacerbation in cysticfibrosis. Thorax 2016; 71: 223–229.https://doi.org/10.1183/23120541.00057-2017 4ORIGINAL RESEARCH LETTER | H.L. BARR ET AL.

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Weight gain during acute treatment of an initial pulmonary exacerbation is associated with a longer interval to the next exacerbation in adults with cystic fibrosis

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