97
Views
9
CrossRef citations to date
0
Altmetric
Review

Novel end points for clinical trials in young children with cystic fibrosis

, , , &
Pages 231-243 | Published online: 09 Jan 2014

References

  • Konstan MW, Hilliard KA, Norvell TM, Berger M. Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am. J. Respir. Crit. Care Med. 150(2), 448–454 (1994).
  • Stick SM, Brennan S, Murray C et al.; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening. J. Pediatr. 155(5), 623–628.e1 (2009).
  • Armstrong DS, Grimwood K, Carlin JB et al. Lower airway inflammation in infants and young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 156(4 Pt 1), 1197–1204 (1997).
  • Dakin CJ, Numa AH, Wang H, Morton JR, Vertzyas CC, Henry RL. Inflammation, infection, and pulmonary function in infants and young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 165(7), 904–910 (2002).
  • Sly PD, Brennan S, Gangell C et al.; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF). Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am. J. Respir. Crit. Care Med. 180(2), 146–152 (2009).
  • Mott LS, Gangell CL, Murray CP, Stick SM, Sly PD; AREST CF. Bronchiectasis in an asymptomatic infant with cystic fibrosis diagnosed following newborn screening. J. Cyst. Fibros. 8(4), 285–287 (2009).
  • Linnane BM, Hall GL, Nolan G et al.; AREST-CF. Lung function in infants with cystic fibrosis diagnosed by newborn screening. Am. J. Respir. Crit. Care Med. 178(12), 1238–1244 (2008).
  • Pillarisetti N, Williamson E, Linnane B et al.; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). Infection, inflammation, and lung function decline in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 184(1), 75–81 (2011).
  • Hoo AF, Thia LP, Nguyen TT et al.; London Cystic Fibrosis Collaboration. Lung function is abnormal in 3-month-old infants with cystic fibrosis diagnosed by newborn screening. Thorax 67(10), 874–881 (2012).
  • Ratjen F, Grasemann H. New therapies in cystic fibrosis. Curr. Pharm. Des. 18(5), 614–627 (2012).
  • Davis SD, Brody AS, Emond MJ, Brumback LC, Rosenfeld M. Endpoints for clinical trials in young children with cystic fibrosis. Proc. Am. Thorac. Soc. 4(4), 418–430 (2007).
  • Sly PD, Brennan S. Detecting early lung disease in cystic fibrosis: are current techniques sufficient? Thorax 59(12), 1008–1010 (2004).
  • Tiddens HA, Donaldson SH, Rosenfeld M, Paré PD. Cystic fibrosis lung disease starts in the small airways: can we treat it more effectively? Pediatr. Pulmonol. 45(2), 107–117 (2010).
  • Gustafsson PM, De Jong PA, Tiddens HA, Lindblad A. Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis. Thorax 63(2), 129–134 (2008).
  • Gustafsson PM. Peripheral airway involvement in CF and asthma compared by inert gas washout. Pediatr. Pulmonol. 42(2), 168–176 (2007).
  • Aurora P, Bush A, Gustafsson P et al.; London Cystic Fibrosis Collaboration. Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 171(3), 249–256 (2005).
  • Gappa M, Ranganathan SC, Stocks J. Lung function testing in infants with cystic fibrosis: lessons from the past and future directions. Pediatr. Pulmonol. 32(3), 228–245 (2001).
  • Lebecque P, Desmond K, Swartebroeckx Y, Dubois P, Lulling J, Coates A. Measurement of respiratory system resistance by forced oscillation in normal children: a comparison with spirometric values. Pediatr. Pulmonol. 10(2), 117–122 (1991).
  • Mortola JP, Frappell PB, Dotta A et al. Ventilatory and metabolic responses to acute hyperoxia in newborns. Am. Rev. Respir. Dis. 146(1), 11–15 (1992).
  • Robinson PD, Goldman MD, Gustafsson PM. Inert gas washout: theoretical background and clinical utility in respiratory disease. Respiration 78(3), 339–355 (2009).
  • Robinson PD, Latzin P, Verbanck S et al. Guidelines for Inert Gas Washout Measurements using Multiple and Single Breath Tests: Recommendations given by experts in the field. Eur. Respir. J. (2012) (In Press).
  • Aurora P, Stanojevic S, Wade A et al.; London Cystic Fibrosis Collaboration. Lung clearance index at 4 years predicts subsequent lung function in children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 183(6), 752–758 (2011).
  • Kraemer R, Blum A, Schibler A, Ammann RA, Gallati S. Ventilation inhomogeneities in relation to standard lung function in patients with cystic fibrosis. Am. J. Respir. Crit. Care Med. 171(4), 371–378 (2005).
  • Robinson PD, Cooper P, Van Asperen P, Fitzgerald D, Selvadurai H. Using index of ventilation to assess response to treatment for acute pulmonary exacerbation in children with cystic fibrosis. Pediatr. Pulmonol. 44(8), 733–742 (2009).
  • Amin R, Subbarao P, Lou W et al. The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis. Eur. Respir. J. 37(4), 806–812 (2011).
  • Amin R, Subbarao P, Jabar A et al. Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax 65(5), 379–383 (2010).
  • Belessis Y, Dixon B, Hawkins G et al. Early cystic fibrosis lung disease detected by bronchoalveolar lavage and lung clearance index. Am. J. Respir. Crit. Care Med. 185(8), 862–873 (2012).
  • Lum S, Gustafsson P, Ljungberg H et al.; London Cystic Fibrosis Collaboration. Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests. Thorax 62(4), 341–347 (2007).
  • Hall GL, Logie KM, Parsons F et al.; AREST CF. Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening. PLoS ONE 6(8), e23932 (2011).
  • Singer F, Stern G, Thamrin C et al. Tidal volume single breath washout of two tracer gases – a practical and promising lung function test. PLoS ONE 6(3), e17588 (2011).
  • Lacquet LM, van Muylem A. He and SF6 single-breath expiration curves. Comparison with the paiva-engel model. Bull. Eur. Physiopathol. Respir. 18(2), 239–246 (1982).
  • Van Muylem A, De Vuyst P, Yernault JC, Paiva M. Inert gas single-breath washout and structural alteration of respiratory bronchioles. Am. Rev. Respir. Dis. 146(5 Pt 1), 1167–1172 (1992).
  • Fuchs O, Latzin P, Thamrin C et al. Normative data for lung function and exhaled nitric oxide in unsedated healthy infants. Eur. Respir. J. 37(5), 1208–1216 (2011).
  • Schibler A, Hall GL, Businger F et al. Measurement of lung volume and ventilation distribution with an ultrasonic flow meter in healthy infants. Eur. Respir. J. 20(4), 912–918 (2002).
  • Viklund E, Lindblad A, Robinson P et al. Comparison of a New Nitrogen Multiple Breath Washout Method to Mass Spectrometer SF6 Washout in Cystic Fibrosis Subjects. European Respiratory Society, Amsterdam, The Netherlands (2011).
  • ATS/ERS Statement. Raised volume forced expirations in infants. Am. J. Respir. Crit. Care Med. 172(11), 1463–1471 (2005).
  • Harrison AN, Regelmann WE, Zirbes JM, Milla CE. Longitudinal assessment of lung function from infancy to childhood in patients with cystic fibrosis. Pediatr. Pulmonol. 44(4), 330–339 (2009).
  • Kozlowska WJ, Bush A, Wade A et al.; London Cystic Fibrosis Collaboration. Lung function from infancy to the preschool years after clinical diagnosis of cystic fibrosis. Am. J. Respir. Crit. Care Med. 178(1), 42–49 (2008).
  • Subbarao P, Balkovec S, Solomon M, Ratjen F. Pilot study of safety and tolerability of inhaled hypertonic saline in infants with cystic fibrosis. Pediatr. Pulmonol. 42(5), 471–476 (2007).
  • Dellon EP, Donaldson SH, Johnson R, Davis SD. Safety and tolerability of inhaled hypertonic saline in young children with cystic fibrosis. Pediatr. Pulmonol. 43(11), 1100–1106 (2008).
  • Rosenfeld M, Ratjen F, Brumback L et al.; ISIS Study Group. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA 307(21), 2269–2277 (2012).
  • Gaffin JM, Shotola NL, Martin TR, Phipatanakul W. Clinically useful spirometry in preschool-aged children: evaluation of the 2007 American Thoracic Society Guidelines. J. Asthma 47(7), 762–767 (2010).
  • Hantos Z, Daróczy B, Suki B, Nagy S, Fredberg JJ. Input impedance and peripheral inhomogeneity of dog lungs. J. Appl. Physiol. 72(1), 168–178 (1992).
  • Brennan S, Hall GL, Horak F et al. Correlation of forced oscillation technique in preschool children with cystic fibrosis with pulmonary inflammation. Thorax 60(2), 159–163 (2005).
  • Oostveen E, MacLeod D, Lorino H et al.; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur. Respir. J. 22(6), 1026–1041 (2003).
  • Beydon N. Pulmonary function testing in young children. Paediatr. Respir. Rev. 10(4), 208–213 (2009).
  • Nielsen KG, Pressler T, Klug B, Koch C, Bisgaard H. Serial lung function and responsiveness in cystic fibrosis during early childhood. Am. J. Respir. Crit. Care Med. 169(11), 1209–1216 (2004).
  • Lebecque P, Stanescu D. Respiratory resistance by the forced oscillation technique in asthmatic children and cystic fibrosis patients. Eur. Respir. J. 10(4), 891–895 (1997).
  • Hellinckx J, De Boeck K, Demedts M. No paradoxical bronchodilator response with forced oscillation technique in children with cystic fibrosis. Chest 113(1), 55–59 (1998).
  • Gangell CL, Horak F Jr, Patterson HJ, Sly PD, Stick SM, Hall GL. Respiratory impedance in children with cystic fibrosis using forced oscillations in clinic. Eur. Respir. J. 30(5), 892–897 (2007).
  • Hall GL, Sly PD, Fukushima T et al. Respiratory function in healthy young children using forced oscillations. Thorax 62(6), 521–526 (2007).
  • Calogero C, Simpson SJ, Lombardi E et al. Respiratory impedance and bronchodilator responsiveness in healthy children aged 2–13 years. Pediatr. Pulmonol. doi:10.1002/ppul.22699 (2012) (Epub ahead of print).
  • Frei J, Jutla J, Kramer G, Hatzakis GE, Ducharme FM, Davis GM. Impulse oscillometry: reference values in children 100 to 150 cm in height and 3 to 10 years of age. Chest 128(3), 1266–1273 (2005).
  • Dencker M, Malmberg LP, Valind S et al. Reference values for respiratory system impedance by using impulse oscillometry in children aged 2–11 years. Clin. Physiol. Funct. Imaging 26(4), 247–250 (2006).
  • Beydon N. Interrupter resistance: what’s feasible? Paediatr. Respir. Rev. 7(Suppl. 1), S5–S7 (2006).
  • Beydon N, Amsallem F, Bellet M et al. Pulmonary function tests in preschool children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 166(8), 1099–1104 (2002).
  • Oswald-Mammosser M, Charloux A, Donato L et al. Interrupter technique versus plethysmography for measurement of respiratory resistance in children with asthma or cystic fibrosis. Pediatr. Pulmonol. 29(3), 213–220 (2000).
  • Lum S. Lung function in preschool children: applications in clinical and epidemiological research. Paediatr. Respir. Rev. 7(Suppl. 1), S30–S32 (2006).
  • Terheggen-Lagro SW, Arets HG, van der Laag J, van der Ent CK. Radiological and functional changes over 3 years in young children with cystic fibrosis. Eur. Respir. J. 30(2), 279–285 (2007).
  • Davies PL, Doull IJ, Child F. The interrupter technique to assess airway responsiveness in children with cystic fibrosis. Pediatr. Pulmonol. 42(1), 23–28 (2007).
  • Davis SD, Rosenfeld M, Kerby GS et al. Multicenter evaluation of infant lung function tests as cystic fibrosis clinical trial endpoints. Am. J. Respir. Crit. Care Med. 182(11), 1387–1397 (2010).
  • Castile RG, Iram D, McCoy KS. Gas trapping in normal infants and in infants with cystic fibrosis. Pediatr. Pulmonol. 37(5), 461–469 (2004).
  • Peterson-Carmichael SL, Harris WT, Goel R et al. Association of lower airway inflammation with physiologic findings in young children with cystic fibrosis. Pediatr. Pulmonol. 44(5), 503–511 (2009).
  • Smyth AR, Walters S. Prophylactic anti-staphylococcal antibiotics for cystic fibrosis. Cochrane Database Syst. Rev. 12, CD001912 (2012).
  • Beardsmore CS, Thompson JR, Williams A et al. Pulmonary function in infants with cystic fibrosis: the effect of antibiotic treatment. Arch. Dis. Child. 71(2), 133–137 (1994).
  • Dab I, Alexander F. A simplified approach to the measurement of specific airway resistance. Pediatr. Res. 10(12), 998–999 (1976).
  • Peslin R, Duvivier C, Malvestio P, Benis AR. Correction of thermal artifacts in plethysmographic airway resistance measurements. J. Appl. Physiol. 80(6), 2198–2203 (1996).
  • Kirkby J, Stanojevic S, Welsh L et al.; Asthma UK. Reference equations for specific airway resistance in children: the Asthma UK initiative. Eur. Respir. J. 36(3), 622–629 (2010).
  • Frey U, Stocks J, Sly P, Bates J. Specification for signal processing and data handling used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society. Eur. Respir. J. 16(5), 1016–1022 (2000).
  • Frey U, Stocks J, Coates A, Sly P, Bates J. Specifications for equipment used for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/ American Thoracic Society. Eur. Respir. J. 16(4), 731–740 (2000).
  • Hansell DM. Bronchiectasis. Radiol. Clin. North Am. 36(1), 107–128 (1998).
  • Robinson TE. Imaging of the chest in cystic fibrosis. Clin. Chest Med. 28(2), 405–421 (2007).
  • Brasfield D, Hicks G, Soong S, Tiller RE. The chest roentgenogram in cystic fibrosis: a new scoring system. Pediatrics 63(1), 24–29 (1979).
  • Conway SP, Pond MN, Bowler I et al. The chest radiograph in cystic fibrosis: a new scoring system compared with the Chrispin–Norman and Brasfield scores. Thorax 49(9), 860–862 (1994).
  • Farrell PM, Li Z, Kosorok MR et al. Longitudinal evaluation of bronchopulmonary disease in children with cystic fibrosis. Pediatr. Pulmonol. 36(3), 230–240 (2003).
  • Li Z, Sanders DB, Rock MJ et al. Regional differences in the evolution of lung disease in children with cystic fibrosis. Pediatr. Pulmonol. 47(7), 635–640 (2012).
  • Loeve M, van Hal PT, Robinson P et al. The spectrum of structural abnormalities on CT scans from patients with CF with severe advanced lung disease. Thorax 64(10), 876–882 (2009).
  • de Jong PA, Ottink MD, Robben SG et al. Pulmonary disease assessment in cystic fibrosis: comparison of CT scoring systems and value of bronchial and arterial dimension measurements. Radiology 231(2), 434–439 (2004).
  • Mott LS, Park J, Murray CP et al.; AREST CF. Progression of early structural lung disease in young children with cystic fibrosis assessed using CT. Thorax 67(6), 509–516 (2012).
  • de Jong PA, Nakano Y, Lequin MH et al. Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis. Eur. Respir. J. 23(1), 93–97 (2004).
  • Davis SD, Fordham LA, Brody AS et al. Computed tomography reflects lower airway inflammation and tracks changes in early cystic fibrosis. Am. J. Respir. Crit. Care Med. 175(9), 943–950 (2007).
  • de Jong PA, Lindblad A, Rubin L et al. Progression of lung disease on computed tomography and pulmonary function tests in children and adults with cystic fibrosis. Thorax 61(1), 80–85 (2006).
  • Brody AS, Klein JS, Molina PL, Quan J, Bean JA, Wilmott RW. High-resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests. J. Pediatr. 145(1), 32–38 (2004).
  • Dakin CJ, Pereira JK, Henry RL, Wang H, Morton JR. Relationship between sputum inflammatory markers, lung function, and lung pathology on high-resolution computed tomography in children with cystic fibrosis. Pediatr. Pulmonol. 33(6), 475–482 (2002).
  • Owens CM, Aurora P, Stanojevic S et al.; London Cystic Fibrosis Collaboration. Lung Clearance Index and HRCT are complementary markers of lung abnormalities in young children with CF. Thorax 66(6), 481–488 (2011).
  • Loeve M, Hop WC, de Bruijne M et al.; Computed Tomography Cystic Fibrosis Survival Study Group. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation. Am. J. Respir. Crit. Care Med. 185(10), 1096–1103 (2012).
  • Tepper LA, Ciet P, Gonzalez-Graniel K et al. Impact of bronchiectasis and trapped air on quality of life in cystic fibrosis lung disease – a CT and MRI comparison. Pediatr. Pulmonol. 46(S34), 340 (2011).
  • Loeve M, Gerbrands K, Hop WC, Rosenfeld M, Hartmann IC, Tiddens HA. Bronchiectasis and pulmonary exacerbations in children and young adults with cystic fibrosis. Chest 140(1), 178–185 (2011).
  • Long FR, Williams RS, Adler BH, Castile RG. Comparison of quiet breathing and controlled ventilation in the high-resolution CT assessment of airway disease in infants with cystic fibrosis. Pediatr. Radiol. 35(11), 1075–1080 (2005).
  • Sargent MA, Jamieson DH, McEachern AM, Blackstock D. Increased inspiratory pressure for reduction of atelectasis in children anesthetized for CT scan. Pediatr. Radiol. 32(5), 344–347 (2002).
  • Wainwright CE, Vidmar S, Armstrong DS et al.; ACFBAL Study Investigators. Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial. JAMA 306(2), 163–171 (2011).
  • de Jong PA, Nakano Y, Lequin MH, Tiddens HA. Dose reduction for CT in children with cystic fibrosis: is it feasible to reduce the number of images per scan? Pediatr. Radiol. 36(1), 50–53 (2006).
  • Goris ML, Robinson TE. Sampling density for the quantitative evaluation of air trapping. Pediatr. Radiol. 39(3), 221–225 (2009).
  • Loeve M, de Bruijne M, Hartmann IC, van Straten M, Hop WC, Tiddens HA. Three-section expiratory CT: insufficient for trapped air assessment in patients with cystic fibrosis? Radiology 262(3), 969–976 (2012).
  • Pearce MS, Salotti JA, Little MP et al. Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet 380(9840), 499–505 (2012).
  • Robinson TE, Long FR, Raman P et al. An airway phantom to standardize CT acquisition in multicenter clinical trials. Acad. Radiol. 16(9), 1134–1141 (2009).
  • Raman P, Raman R, Newman B, Venkatraman R, Raman B, Robinson TE. Development and validation of automated 2D-3D bronchial airway matching to track changes in regional bronchial morphology using serial low-dose chest CT scans in children with chronic lung disease. J. Digit. Imaging 23(6), 744–754 (2010).
  • Bagci U, Yao J, Caban J, Palmore TN, Suffredini AF, Mollura DJ. Automatic detection of tree-in-bud patterns for computer assisted diagnosis of respiratory tract infections. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011, 5096–5099 (2011).
  • Goris ML, Zhu HJ, Blankenberg F, Chan F, Robinson TE. An automated approach to quantitative air trapping measurements in mild cystic fibrosis. Chest 123(5), 1655–1663 (2003).
  • Busacker A, Newell JD Jr, Keefe T et al. A multivariate analysis of risk factors for the air-trapping asthmatic phenotype as measured by quantitative CT analysis. Chest 135(1), 48–56 (2009).
  • Puderbach M, Eichinger M, Gahr J et al. Proton MRI appearance of cystic fibrosis: comparison to CT. Eur. Radiol. 17(3), 716–724 (2007).
  • Altes TA, Eichinger M, Puderbach M. Magnetic resonance imaging of the lung in cystic fibrosis. Proc. Am. Thorac. Soc. 4(4), 321–327 (2007).
  • Puderbach M, Eichinger M. The role of advanced imaging techniques in cystic fibrosis follow-up: is there a place for MRI? Pediatr. Radiol. 40(6), 844–849 (2010).
  • Eichinger M, Optazaite DE, Kopp-Schneider A et al. Morphologic and functional scoring of cystic fibrosis lung disease using MRI. Eur. J. Radiol. 81(6), 1321–1329 (2012).
  • Failo R, Wielopolski PA, Tiddens HA, Hop WC, Mucelli RP, Lequin MH. Lung morphology assessment using MRI: a robust ultra-short TR/TE 2D steady state free precession sequence used in cystic fibrosis patients. Magn. Reson. Med. 61(2), 299–306 (2009).
  • Ngan DA, Wilcox PG, Aldaabil M et al. The relationship of systemic inflammation to prior hospitalization in adult patients with cystic fibrosis. BMC Pulm. Med. 12, 3 (2012).
  • Levy H, Kalish LA, Huntington I et al. Inflammatory markers of lung disease in adult patients with cystic fibrosis. Pediatr. Pulmonol. 42(3), 256–262 (2007).
  • Nixon LS, Yung B, Bell SC, Elborn JS, Shale DJ. Circulating immunoreactive interleukin-6 in cystic fibrosis. Am. J. Respir. Crit. Care Med. 157(6 Pt 1), 1764–1769 (1998).
  • Bell B, Nixon M, Elborn S. Metabolic and inflammatory responses to pulmonary exacerbation in adults with cystic fibrosis. Eur. J. Clin. Investig. 30(6), 553–559 (2000).
  • Proesmans M, Els C, Vermeulen F, De Boeck K. Change in IgG and evolution of lung function in children with cystic fibrosis. J. Cyst. Fibros. 10(2), 128–131 (2011).
  • Wheeler WB, Williams M, Matthews WJ Jr, Colten HR. Progression of cystic fibrosis lung disease as a function of serum immunoglobulin G levels: a 5-year longitudinal study. J. Pediatr. 104(5), 695–699 (1984).
  • Norman D, Elborn JS, Cordon SM et al. Plasma tumour necrosis factor α in cystic fibrosis. Thorax 46(2), 91–95 (1991).
  • Harris WT, Muhlebach MS, Oster RA, Knowles MR, Clancy JP, Noah TL. Plasma TGF-β1 in pediatric cystic fibrosis: potential biomarker of lung disease and response to therapy. Pediatr. Pulmonol. 46(7), 688–695 (2011).
  • Lagrange-Puget M, Durieu I, Ecochard R et al. Longitudinal study of oxidative status in 312 cystic fibrosis patients in stable state and during bronchial exacerbation. Pediatr. Pulmonol. 38(1), 43–49 (2004).
  • Wolter J, Seeney S, Bell S, Bowler S, Masel P, McCormack J. Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Thorax 57(3), 212–216 (2002).
  • Ollero M, Astarita G, Guerrera IC et al. Plasma lipidomics reveals potential prognostic signatures within a cohort of cystic fibrosis patients. J. Lipid Res. 52(5), 1011–1022 (2011).
  • Bruce MC, Poncz L, Klinger JD, Stern RC, Tomashefski JF Jr, Dearborn DG. Biochemical and pathologic evidence for proteolytic destruction of lung connective tissue in cystic fibrosis. Am. Rev. Respir. Dis. 132(3), 529–535 (1985).
  • Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis. Eur. Respir. J. 40(4), 969–976 (2012).
  • Laguna TA, Wagner BD, Starcher B et al. Urinary desmosine: a biomarker of structural lung injury during CF pulmonary exacerbation. Pediatric Pulmonol. 47(9), 856–863 (2012).
  • Mayer-Hamblett N, Aitken ML, Accurso FJ et al. Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am. J. Respir. Crit. Care Med. 175(8), 822–828 (2007).
  • Sagel SD, Chmiel JF, Konstan MW. Sputum biomarkers of inflammation in cystic fibrosis lung disease. Proc. Am. Thorac. Soc. 4(4), 406–417 (2007).
  • de Blic J, Midulla F, Barbato A et al.; European Respiratory Society. Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. Eur. Respir. J. 15(1), 217–231 (2000).
  • Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 151(4), 1075–1082 (1995).
  • Rosenfeld M, Gibson RL, McNamara S et al. Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr. Pulmonol. 32(5), 356–366 (2001).
  • Nixon GM, Armstrong DS, Carzino R et al. Early airway infection, inflammation, and lung function in cystic fibrosis. Arch. Dis. Child. 87(4), 306–311 (2002).
  • Esther CR Jr, Alexis NE, Clas ML et al. Extracellular purines are biomarkers of neutrophilic airway inflammation. Eur. Respir. J. 31(5), 949–956 (2008).
  • Armstrong DS, Hook SM, Jamsen KM et al. Lower airway inflammation in infants with cystic fibrosis detected by newborn screening. Pediatr. Pulmonol. 40(6), 500–510 (2005).
  • Meyer KC, Sharma A. Regional variability of lung inflammation in cystic fibrosis. Am. J. Respir. Crit. Care Med. 156(5), 1536–1540 (1997).
  • Gutierrez JP, Grimwood K, Armstrong DS et al. Interlobar differences in bronchoalveolar lavage fluid from children with cystic fibrosis. Eur. Respir. J. 17(2), 281–286 (2001).
  • Gangell C, Gard S, Douglas T et al.; AREST CF. Inflammatory responses to individual microorganisms in the lungs of children with cystic fibrosis. Clin. Infect. Dis. 53(5), 425–432 (2011).
  • Gibson RL, Emerson J, McNamara S et al.; Cystic Fibrosis Therapeutics Development Network Study Group. Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 167(6), 841–849 (2003).
  • Rosenfeld M, Gibson R, McNamara S et al. Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis. J. Pediatr. 139(4), 572–577 (2001).
  • Wagener JS, Rock MJ, McCubbin MM, Hamilton SD, Johnson CA, Ahrens RC. Aerosol delivery and safety of recombinant human deoxyribonuclease in young children with cystic fibrosis: a bronchoscopic study. Pulmozyme Pediatric Broncoscopy Study Group. J. Pediatr. 133(4), 486–491 (1998).
  • Horváth I, Hunt J, Barnes PJ et al.; ATS/ERS Task Force on Exhaled Breath Condensate. Exhaled breath condensate: methodological recommendations and unresolved questions. Eur. Respir. J. 26(3), 523–548 (2005).
  • Effros RM, Dunning MB 3rd, Biller J, Shaker R. The promise and perils of exhaled breath condensates. Am. J. Physiol. Lung Cell Mol. Physiol. 287(6), L1073–L1080 (2004).
  • Effros RM, Biller J, Foss B et al. A simple method for estimating respiratory solute dilution in exhaled breath condensates. Am. J. Respir. Crit. Care Med. 168(12), 1500–1505 (2003).
  • Robroeks CM, Rosias PP, van Vliet D et al. Biomarkers in exhaled breath condensate indicate presence and severity of cystic fibrosis in children. Pediatr. Allergy Immunol. 19(7), 652–659 (2008).
  • Robroeks CM, Jöbsis Q, Damoiseaux JG et al. Cytokines in exhaled breath condensate of children with asthma and cystic fibrosis. Ann. Allergy Asthma Immunol. 96(2), 349–355 (2006).
  • Bodini A, D’Orazio C, Peroni DG et al. IL-8 and pH values in exhaled condensate after antibiotics in cystic fibrosis children. Int. J. Immunopathol. Pharmacol. 20(3), 467–472 (2007).
  • Bodini A, D’Orazio C, Peroni D et al. Biomarkers of neutrophilic inflammation in exhaled air of cystic fibrosis children with bacterial airway infections. Pediatr. Pulmonol. 40(6), 494–499 (2005).
  • Lucidi V, Ciabattoni G, Bella S, Barnes PJ, Montuschi P. Exhaled 8-isoprostane and prostaglandin E2 in patients with stable and unstable cystic fibrosis. Free Radic. Biol. Med. 45(6), 913–919 (2008).
  • Dressel H, Müller F, Fischer R et al. Independent information of nonspecific biomarkers in exhaled breath condensate. Respiration. 80(5), 401–409 (2010).
  • Formanek W, Inci D, Lauener RP, Wildhaber JH, Frey U, Hall GL. Elevated nitrite in breath condensates of children with respiratory disease. Eur. Respir. J. 19(3), 487–491 (2002).
  • Carpagnano GE, Barnes PJ, Geddes DM, Hodson ME, Kharitonov SA. Increased leukotriene B4 and interleukin-6 in exhaled breath condensate in cystic fibrosis. Am. J. Respir. Crit. Care Med. 167(8), 1109–1112 (2003).
  • Esther CR Jr, Boysen G, Olsen BM et al. Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol. 296(6), L987–L993 (2009).
  • Ojoo JC, Mulrennan SA, Kastelik JA, Morice AH, Redington AE. Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis. Thorax 60(1), 22–26 (2005).
  • Carpagnano GE, Barnes PJ, Francis J, Wilson N, Bush A, Kharitonov SA. Breath condensate pH in children with cystic fibrosis and asthma: a new noninvasive marker of airway inflammation? Chest 125(6), 2005–2010 (2004).
  • Tate S, MacGregor G, Davis M, Innes JA, Greening AP. Airways in cystic fibrosis are acidified: detection by exhaled breath condensate. Thorax 57(11), 926–929 (2002).
  • Moeller A, Franklin P, Hall GL, Horak F Jr, Wildhaber JH, Stick SM. Measuring exhaled breath condensates in infants. Pediatr. Pulmonol. 41(2), 184–187 (2006).
  • Muller WG, Morini F, Eaton S, Peters M, Jaffe A. Safety and feasibility of exhaled breath condensate collection in ventilated infants and children. Eur. Respir. J. 28(3), 479–485 (2006).
  • Patel K, Davis SD, Johnson R, Esther CR Jr. Exhaled breath condensate purines correlate with lung function in infants and preschoolers. Pediatr. Pulmonol. 48(2), 182–187 (2013).
  • Barker M, Hengst M, Schmid J et al. Volatile organic compounds in the exhaled breath of young patients with cystic fibrosis. Eur. Respir. J. 27(5), 929–936 (2006).
  • Robroeks CM, van Berkel JJ, Dallinga JW et al. Metabolomics of volatile organic compounds in cystic fibrosis patients and controls. Pediatr. Res. 68(1), 75–80 (2010).
  • Dragonieri S, Schot R, Mertens BJ et al. An electronic nose in the discrimination of patients with asthma and controls. J. Allergy Clin. Immunol. 120(4), 856–862 (2007).
  • de Benedictis FM, Guidi R, Carraro S, Baraldi E; TEDDY European Network of Excellence. Endpoints in respiratory diseases. Eur. J. Clin. Pharmacol. 67(Suppl. 1), 49–59 (2011).
  • Tiret L, Nivoche Y, Hatton F, Desmonts JM, Vourc’h G. Complications related to anaesthesia in infants and children. A prospective survey of 40240 anaesthetics. Br. J. Anaesth. 61(3), 263–269 (1988).
  • Hoffman GM. Outcomes of pediatric anesthesia. Semin. Pediatr. Surg. 17(2), 141–151 (2008).
  • Sun L. Early childhood general anaesthesia exposure and neurocognitive development. Br. J. Anaesth. 105(Suppl. 1), i61–i68 (2010).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.