S3-Leitlinie: Lungenerkrankung bei Mukoviszidose – Pseudomonas aeruginosa

Zusammenfassung

Mukoviszidose (Cystic Fibrosis, CF) ist die häufigste autosomal-rezessiv vererbte Multisystemerkrankung. In Deutschland sind mind. 8000 Menschen betroffen. Die Erkrankung wird durch Mutationen im Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Gen verursacht, welche zu einer Fehlfunktion des Chloridkanals CFTR führen. Dadurch kommt es in den Atemwegen zu einer unzureichenden Hydrierung des epithelialen Flüssigkeitsfilms und somit zu einer Reduktion der mukoziliären Clearance.

Auch wenn seit einigen Jahren mit der CFTR-Modulatortherapie eine hochwirksame kausale CF-Therapie zur Verfügung steht und die Patienten größtenteils das höhere Erwachsenenalter erreichen, treten rezidivierende und chronische Infektionen der Atemwege sowie pulmonale Exazerbationen weiterhin auf. Im Erwachsenenalter zeigt sich v. a. die Kolonisation und chronische Infektion mit Pseudomonas aeruginosa (PA), die zu weiterem Verlust an Lungenfunktion führt. Für die medikamentöse Therapie der chronischen PA-Infektion stehen viele unterschiedliche Therapieoptionen zur Verfügung.

Mit dieser S3-Leitlinie wird eine evidenzbasierte Diagnostik und Therapie der PA-Infektion dargelegt, um eine Orientierung bei der individuellen Therapieentscheidung zu geben.

Abstract

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the airway epithelial lining fluid which leads to reduction of the mucociliary clearance.

Even if highly effective, CFTR modulator therapy has been available for some years and people with CF are getting much older than before, recurrent and chronic infections of the airways as well as pulmonary exacerbations still occur. In adult CF life, Pseudomonas aeruginosa (PA) is the most relevant pathogen in colonisation and chronic infection of the lung, leading to further loss of lung function. There are many possibilities to treat PA-infection.

This is a S3-clinical guideline which implements a definition for chronic PA-infection and demonstrates evidence-based diagnostic methods and medical treatment in order to give guidance for individual treatment options.

^a Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP), federführende Fachgesellschaft

^b Mukoviszidose Institut gGmbH (MI)

^c Deutsche Gesellschaft für Kinder- und Jugendmedizin e. V. (DGKJ)

^d Deutsche Gesellschaft für Hygiene und Mikrobiologie e. V. (DGHM)

^e Deutsche Gesellschaft für Pädiatrische Infektiologie e. V. (DGPI)

^f Deutsche Röntgengesellschaft e. V. (DRG)

^g Gesellschaft für Pädiatrische Pneumologie e. V. (GPP), federführende Fachgesellschaft

^h Deutsche Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie e. V. (DGHNO)

ⁱ Allianz Chronischer Seltener Erkrankungen (ACHSE)

^j Österreichische Gesellschaft für Pneumologie (ÖGP)

^k Österreichische Gesellschaft für Kinder- und Jugendheilkunde (ÖGKJ)

^l Mukoviszidose e. V.

^m Gesellschaft für Pädiatrische Radiologie (GPR)

ⁿ Deutsche Gesellschaft für Infektiologie e. V. (DGI)

^o Deutscher Verband für Physiotherapie (ZVK) e. V.

Publication History

Article published online:
13 February 2024

• Literatur

• 1 Nährlich L, Burkhart M, Wosniok J. Deutsches Mukoviszidose-Register – Berichtsband 2021. 2022
• 2 Müller F-M, Bend J, Rietschel E. et al. S3-Leitlinie „Lungenerkrankung bei Mukoviszidose“, Modul 1: Diagnostik und Therapie nach dem ersten Nachweis von Pseudomonas aeruginosa. AWMF; 2012
• 3 Schwarz C. 020-018 Lungenerkrankung bei Mukoviszidose. Modul 2: Chronische Pseudomonas-Infektion. AWMF Leitlinie; 2017
• 4 Nährlich L, Stuhrmann-Spangenberg M, Barben J. et al. S2k-Leitlinie „Diagnose der Mukovsizidose“. AWMF; 2013
• 5 Hammermann J, Claßen M, Schmidt S. et al. S3-Leitlinie: Mukoviszidose bei Kindern in den ersten beiden Lebensjahren, Diagnostik und Therapie. AWMF; 2020
• 6 Heltshe SL, Mayer-Hamblett N, Burns JL. et al. Pseudomonas aeruginosa in cystic fibrosis patients with G551D-CFTR treated with ivacaftor. Clin Infect Dis 2015; 60: 703-712
• 7 Davies JC, Martin I. New anti-pseudomonal agents for cystic fibrosis – still needed in the era of small molecule CFTR modulators?. Expert Opin Pharmacother 2018; 19: 1327-1336
• 8 Pressler T, Bohmova C, Conway S. et al. Chronic Pseudomonas aeruginosa infection definition: EuroCareCF Working Group report. J Cyst Fibros 2011; 10 (Suppl. 02) S75-S78
• 9 Lee TW, Brownlee KG, Conway SP. et al. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003; 2: 29-34
• 10 Mainz J, Lindig JSM, Wiedemann B. et al. Dynamics of upper and lower airway colonization with P. aeruginosa and S. aureus in CF-patients within 3.5 years. Journal of Cystic Fibrosis 2009; 8: S64
• 11 Mainz JG, Naehrlich L, Schien M. et al. Concordant genotype of upper and lower airways P aeruginosa and S aureus isolates in cystic fibrosis. Thorax 2009; 64: 535-540
• 12 Deschaght P, De Baere T, Van Simaey L. et al. Comparison of the sensitivity of culture, PCR and quantitative real-time PCR for the detection of Pseudomonas aeruginosa in sputum of cystic fibrosis patients. BMC Microbiol 2009; 9: 244
• 13 Littlewood J, CF Trust. Pseudomonas aeruginosa infection in people with cystic fibrosis, suggestions for prevention and infection control 2004; second edition.
• 14 Doring G, Hoiby N. Early intervention and prevention of lung disease in cystic fibrosis: a European consensus. J Cyst Fibros 2004; 3: 67-91
• 15 Ratjen F, Döring G, Nikolaizik WH. Effect of inhaled tobramycin on early Pseudomona aeruginosa colonisation in patients with cystic fibrosis. Lancet 2001; 358: 983-984
• 16 Nicolai T. Pediatric bronchoscopy. Pediatr Pulmonol 2001; 31: 150-164
• 17 Bilton D, Canny G, Conway S. et al. Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J Cyst Fibros 2011; 10 (Suppl. 02) S79-S81
• 18 Breen L, Aswani N. Elective versus symptomatic intravenous antibiotic therapy for cystic fibrosis. Cochrane Database Syst Rev 2012; 7: CD002767
• 19 Vandevanter DR, Yegin A, Morgan WJ. et al. Design and powering of cystic fibrosis clinical trials using pulmonary exacerbation as an efficacy endpoint. J Cyst Fibros 2011; 10: 453-459
• 20 Douglas TA, Brennan S, Berry L. et al. Value of serology in predicting Pseudomonas aeruginosa infection in young children with cystic fibrosis. Thorax 2010; 65: 985-990
• 21 Anstead M, Heltshe SL, Khan U. et al. Pseudomonas aeruginosa serology and risk for re-isolation in the EPIC trial. J Cyst Fibros 2013; 12: 147-153
• 22 Lee VT, Smith RS, Tummler B. et al. Activities of Pseudomonas aeruginosa effectors secreted by the Type III secretion system in vitro and during infection. Infect Immun 2005; 73: 1695-1705
• 23 Mauch RM, Levy CE. Serum antibodies to Pseudomonas aeruginosa in cystic fibrosis as a diagnostic tool: A systematic review. J Cyst Fibros 2014; 13: 499-507
• 24 Kotnik Pirs A, Krivec U, Simcic S. et al. Assessment of serology and spirometry and the combination of both to complement microbiological isolation for earlier detection of Pseudomonas aeruginosa infection in children with cystic fibrosis. BMC pulmonary medicine 2016; 16: 161
• 25 Ratjen F, Walter H, Haug M. et al. Diagnostic value of serum antibodies in early Pseudomonas aeruginosa infection in cystic fibrosis patients. Pediatr Pulmonol 2007; 42: 249-255
• 26 Pressler T, Karpati F, Granstrom M. et al. Diagnostic significance of measurements of specific IgG antibodies to Pseudomonas aeruginosa by three different serological methods. J Cyst Fibros 2009; 8: 37-42
• 27 Kappler M, Nagel F, Feilcke M. et al. Predictive values of antibodies against Pseudomonas aeruginosa in patients with cystic fibrosis one year after early eradication treatment. J Cyst Fibros 2014; 13: 534-541
• 28 Johansen HK, Norregaard L, Gotzsche PC. et al. Antibody response to Pseudomonas aeruginosa in cystic fibrosis patients: a marker of therapeutic success? – A 30-year cohort study of survival in Danish CF patients after onset of chronic P. aeruginosa lung infection. Pediatr Pulmonol 2004; 37: 427-432
• 29 Smyth AR, Bell SC, Bojcin S. et al. European Cystic Fibrosis Society Standards of Care: Best Practice guidelines. J Cyst Fibros 2014; 13S1: S23-S42
• 30 NICE. Cystic Fibrosis: Diagnosis and management. Cystic Fibrosis: Diagnosis and management. London: 2017
• 31 Al-Saleh S, Dell SD, Grasemann H. et al. Sputum induction in routine clinical care of children with cystic fibrosis. J Pediatr 2010; 157: 1006-1011e1
• 32 Ho SA, Ball R, Morrison LJ. et al. Clinical value of obtaining sputum and cough swab samples following inhaled hypertonic saline in children with cystic fibrosis. Pediatr Pulmonol 2004; 38: 82-87
• 33 Hoppe JE, Towler E, Wagner BD. et al. Sputum induction improves detection of pathogens in children with cystic fibrosis. Pediatr Pulmonol 2015; 50: 638-646
• 34 Ramsey BW, Wentz KR, Smith AL. et al. Predictive value of oropharyngeal cultures for identifying lower airway bacteria in cystic fibrosis patients. The American review of respiratory disease 1991; 144: 331-337
• 35 Avital A, Uwyyed K, Picard E. et al. Sensitivity and specificity of oropharyngeal suction versus bronchoalveolar lavage in identifying respiratory tract pathogens in children with chronic pulmonary infection. Pediatr Pulmonol 1995; 20: 40-43
• 36 Wainwright CE, Vidmar S, Armstrong DS. et al. Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial. JAMA 2011; 306: 163-171
• 37 Hogardt M, Podbielski A, Abele-Horn M. et al. MIQ 24 Atemwegsinfektionen bei Mukoviszidose – Qualitätsstandards in der mikrobiologisch-infektiologischen Diagnostik. München: Elsevier; 2019
• 38 Podbielski A, Herrmann M, Kniehl E. et al. MiQ 7 Infektionen der tiefen Atemwege, Teil I+II. Mikrobiologisch-infektiologische Qualitätsstandards, im Auftrag der DGHM. München, Jena: Urban & Fischer; 2010
• 39 Nelson A, De Soyza A, Bourke SJ. et al. Assessment of sample handling practices on microbial activity in sputum samples from patients with cystic fibrosis. Letters in applied microbiology 2010; 51: 272-277
• 40 Gould FK, Freeman R, Hudson S. et al. Does storage of sputum specimens adversely affect culture results?. J Clin Pathol 1996; 49: 684-686
• 41 Pye A, Hill SL, Bharadwa P. et al. Effect of storage and postage on recovery and quantitation of bacteria in sputum samples. J Clin Pathol 2008; 61: 352-354
• 42 Bundesärztekammer. Diskussionsentwurf zu einer Richtlinie zur Präimplantationsdiagnostik. Zeitschrift für Medizinische Ethik 2000; 46: 161-169
• 43 15189:2014-11 DEI. Medizinische Laboratorien Anforderungen an die Qualität und Kompetenz (ISO 15189:2012, korrigierte Fassung 2014-08-15) Deutsche Fassung EN ISO 15189:2012. 2014
• 44 Ordonez CL, Stulbarg M, Grundland H. et al. Effect of clarithromycin on airway obstruction and inflammatory markers in induced sputum in cystic fibrosis: a pilot study. Pediatr Pulmonol 2001; 32: 29-37
• 45 Sagel SD, Kapsner R, Osberg I. et al. Airway inflammation in children with cystic fibrosis and healthy children assessed by sputum induction. Am J Respir Crit Care Med 2001; 164: 1425-1431
• 46 Ahmed B, Bush A, Davies JC. How to use: bacterial cultures in diagnosing lower respiratory tract infections in cystic fibrosis. Archives of disease in childhood Education and practice edition 2014; 99: 181-187
• 47 Bjarnsholt T, Nielsen XC, Johansen U. et al. Methods to classify bacterial pathogens in cystic fibrosis. Methods Mol Biol 2011; 742: 143-171
• 48 Alby K, Gilligan PH, Miller MB. Comparison of matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry platforms for the identification of gram-negative rods from patients with cystic fibrosis. J Clin Microbiol 2013; 51: 3852-3854
• 49 Marko DC, Saffert RT, Cunningham SA. et al. Evaluation of the Bruker Biotyper and Vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry systems for identification of nonfermenting gram-negative bacilli isolated from cultures from cystic fibrosis patients. J Clin Microbiol 2012; 50: 2034-2039
• 50 Com G, Carroll JL, Castro MM. et al. Predictors and outcome of low initial forced expiratory volume in 1 second measurement in children with cystic fibrosis. J Pediatr 2014; 164: 832-838
• 51 Blanchard AC, Rooney AM, Yau Y. et al. Early detection using qPCR of Pseudomonas aeruginosa infection in children with cystic fibrosis undergoing eradication treatment. J Cyst Fibros 2018; 17: 723-728
• 52 Boutin S, Weitnauer M, Hassel S. et al. One time quantitative PCR detection of Pseudomonas aeruginosa to discriminate intermittent from chronic infection in cystic fibrosis. J Cyst Fibros 2018; 17: 348-355
• 53 Burns JL, Rolain JM. Culture-based diagnostic microbiology in cystic fibrosis: can we simplify the complexity?. J Cyst Fibros 2014; 13: 1-9
• 54 Kenna DTD, Lilley D, Coward A. et al. Prevalence of Burkholderia species, including members of Burkholderia cepacia complex, among UK cystic and non-cystic fibrosis patients. J Med Microbiol 2017; 66: 490-501
• 55 Nährlich L, Burkhart M, Wosniok J. Deutsches Mukoviszidose-Register. Berichtsband 2017. Mukoviszidose e. V. & Mukoviszidose Institut gGmbH; 2018
• 56 Spilker T, Vandamme P, Lipuma JJ. Identification and distribution of Achromobacter species in cystic fibrosis. J Cyst Fibros 2013; 12: 298-301
• 57 Schmoldt S, Latzin P, Heesemann J. et al. Clonal analysis of Inquilinus limosus isolates from six cystic fibrosis patients and specific serum antibody response. J Med Microbiol 2006; 55: 1425-1433
• 58 Lambiase A, Catania MR, Del Pezzo M. et al. Achromobacter xylosoxidans respiratory tract infection in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 2011; 30: 973-980
• 59 Degand N, Lotte R, Deconde Le Butor C. et al. Epidemic spread of Pandoraea pulmonicola in a cystic fibrosis center. BMC infectious diseases 2015; 15: 583
• 60 Foweraker JE, Laughton CR, Brown DF. et al. Phenotypic variability of Pseudomonas aeruginosa in sputa from patients with acute infective exacerbation of cystic fibrosis and its impact on the validity of antimicrobial susceptibility testing. J Antimicrob Chemother 2005; 55: 921-927
• 61 Hurley MN, Ariff AH, Bertenshaw C. et al. Results of antibiotic susceptibility testing do not influence clinical outcome in children with cystic fibrosis. J Cyst Fibros 2012; 11: 288-292
• 62 Moskowitz SM, Emerson JC, McNamara S. et al. Randomized trial of biofilm testing to select antibiotics for cystic fibrosis airway infection. Pediatr Pulmonol 2011; 46: 184-192
• 63 Foweraker JE, Laughton CR, Brown DF. et al. Comparison of methods to test antibiotic combinations against heterogeneous populations of multiresistant Pseudomonas aeruginosa from patients with acute infective exacerbations in cystic fibrosis. Antimicrob Agents Chemother 2009; 53: 4809-4815
• 64 Canton R, Maiz L, Escribano A. et al. Spanish consensus on the prevention and treatment of Pseudomonas aeruginosa bronchial infections in cystic fibrosis patients. Archivos de bronconeumologia 2015; 51: 140-150
• 65 Mayer-Hamblett N, Ramsey BW, Kulasekara HD. et al. Pseudomonas aeruginosa phenotypes associated with eradication failure in children with cystic fibrosis. Clin Infect Dis 2014; 59: 624-631
• 66 Schelstraete P, Haerynck F, Van daele S. et al. Eradication therapy for Pseudomonas aeruginosa colonization episodes in cystic fibrosis patients not chronically colonized by P. aeruginosa. J Cyst Fibros 2013; 12: 1-8
• 67 Somayaji R, Parkins MD, Shah A. et al. Antimicrobial susceptibility testing (AST) and associated clinical outcomes in individuals with cystic fibrosis: A systematic review. J Cyst Fibros 2019; 18: 236-243
• 68 Aaron SD, Vandemheen KL, Ferris W. et al. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. Lancet 2005; 366: 463-471
• 69 Waters V, Ratjen F. Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis. Cochrane Database Syst Rev 2017; 6: CD006961
• 70 Doring G, Flume P, Heijerman H. et al. Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J Cyst Fibros 2012; 11: 461-479
• 71 Morosini MI, Garcia-Castillo M, Loza E. et al. Breakpoints for predicting Pseudomonas aeruginosa susceptibility to inhaled tobramycin in cystic fibrosis patients: use of high-range Etest strips. J Clin Microbiol 2005; 43: 4480-4485
• 72 Burns JL, Saiman L, Whittier S. et al. Comparison of two commercial systems (Vitek and MicroScan-WalkAway) for antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis patients. Diagn Microbiol Infect Dis 2001; 39: 257-260
• 73 Balke B, Hoy L, Weissbrodt H. et al. Comparison of the Micronaut Merlin automated broth microtiter system with the standard agar dilution method for antimicrobial susceptibility testing of mucoid and nonmucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients. Eur J Clin Microbiol Infect Dis 2004; 23: 765-771
• 74 Burns JL, Saiman L, Whittier S. et al. Comparison of agar diffusion methodologies for antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis patients. J Clin Microbiol 2000; 38: 1818-1822
• 75 Bradbury RS, Tristram SG, Roddam LF. et al. Antimicrobial susceptibility testing of cystic fibrosis and non-cystic fibrosis clinical isolates of Pseudomonas aeruginosa: a comparison of three methods. Br J Biomed Sci 2011; 68: 1-4
• 76 Dales L, Ferris W, Vandemheen K. et al. Combination antibiotic susceptibility of biofilm-grown Burkholderia cepacia and Pseudomonas aeruginosa isolated from patients with pulmonary exacerbations of cystic fibrosis. Eur J Clin Microbiol Infect Dis 2009; 28: 1275-1279
• 77 Moskowitz SM, Foster JM, Emerson JC. et al. Use of Pseudomonas biofilm susceptibilities to assign simulated antibiotic regimens for cystic fibrosis airway infection. J Antimicrob Chemother 2005; 56: 879-886
• 78 Yau YC, Ratjen F, Tullis E. et al. Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients. J Cyst Fibros 2015; 14: 262-266
• 79 Kirchner S, Fothergill JL, Wright EA. et al. Use of artificial sputum medium to test antibiotic efficacy against Pseudomonas aeruginosa in conditions more relevant to the cystic fibrosis lung. Journal of visualized experiments: JoVE 2012; e3857
• 80 Macia MD, Borrell N, Perez JL. et al. Detection and susceptibility testing of hypermutable Pseudomonas aeruginosa strains with the Etest and disk diffusion. Antimicrob Agents Chemother 2004; 48: 2665-2672
• 81 Mowat E, Paterson S, Fothergill JL. et al. Pseudomonas aeruginosa population diversity and turnover in cystic fibrosis chronic infections. Am J Respir Crit Care Med 2011; 183: 1674-1679
• 82 Simon A. Anforderungen an die Hygiene bei der medizinischen Versorgung von Patienten mit Cystischer Fibrose (Mukoviszidose). 2012
• 83 Kerem E, Conway S, Elborn S. et al. Standards of care for patients with cystic fibrosis: a European consensus. J Cyst Fibros 2005; 4: 7-26
• 84 Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut (RKI). Hygienemaßnahmen bei Infektionen oder Besiedlung mit multiresistenten gramnegativen Stäbchen. Bundesgesundheitsbl  2012; 55: 1311-1354
• 85 Castellani C, Duff AJA, Bell SC. et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros 2018; 17: 153-178
• 86 Langton Hewer SC, Smyth AR. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev 2017; 4: CD004197
• 87 Valerius NH, Koch C, Hoiby N. Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet 1991; 338: 725-726
• 88 Wiesemann HG, Steinkamp G, Ratjen F. et al. Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis. Pediatr Pulmonol 1998; 25: 88-92
• 89 Gibson RL, Emerson J, McNamara S. et al. Significant microbiological effect of inhaled tobramycin in young children with cystic fibrosis. Am J Respir Crit Care Med 2003; 167: 841-849
• 90 Proesmans M, Vermeulen F, Boulanger L. et al. Comparison of two treatment regimens for eradication of Pseudomonas aeruginosa infection in children with cystic fibrosis. J Cyst Fibros 2013; 12: 29-34
• 91 Ratjen F, Munck A, Kho P. et al. Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax 2010; 65: 286-291
• 92 Treggiari MM, Rosenfeld M, Mayer-Hamblett N. et al. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational studyʼ. Contemp Clin Trials 2009; 30: 256-268
• 93 Treggiari MM, Retsch-Bogart G, Mayer-Hamblett N. et al. Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis. Arch Pediatr Adolesc Med 2011; 165: 847-856
• 94 Taccetti G, Bianchini E, Cariani L. et al. Early antibiotic treatment for Pseudomonas aeruginosa eradication in patients with cystic fibrosis: a randomised multicentre study comparing two different protocols. Thorax 2016; 67: 853-859
• 95 Ratien FN, Alon R, Maykut C. et al. WS01.2 TOBI® for eradication of early P. aeruginosa infection in paediatric cystic fibrosis patients: the EARLY study. Journal of Cystic Fibrosis 2016; 15 (Suppl. 01) S00
• 96 Ratjen F, Moeller A, McKinney ML. et al. Eradication of early P. aeruginosa infection in children < 7years of age with cystic fibrosis: The early study. J Cyst Fibros 2019; 18: 78-85
• 97 Hewer SCL, Smyth AR, Brown M. et al. Intravenous versus oral antibiotics for eradication of Pseudomonas aeruginosa in cystic fibrosis (TORPEDO-CF): a randomised controlled trial. Lancet Respir Med 2020; 8: 975-986
• 98 Munck A, Bonacorsi S, Mariani-Kurkdjian P. et al. Genotypic characterization of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonization. Pediatr Pulmonol 2001; 32: 288-292
• 99 Douglas TA, Brennan S, Gard S. et al. Acquisition and eradication of P. aeruginosa in young children with cystic fibrosis. Eur Respir J 2009; 33: 305-311
• 100 Kenny SL, Shaw TD, Downey DG. et al. Eradication of Pseudomonas aeruginosa in adults with cystic fibrosis. BMJ open respiratory research 2014; 1: e000021
• 101 Hoiby N, Frederiksen B, Pressler T. Eradication of early Pseudomonas aeruginosa infection. J Cyst Fibros 2005; 4 (Suppl. 02) 49-54
• 102 Frederiksen B, Koch C, Hoiby N. Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol 1997; 23: 330-335
• 103 Noah TL, Ivins SS, Abode KA. et al. Inhaled versus systemic antibiotics and airway inflammation in children with cystic fibrosis and Pseudomonas. Pediatr Pulmonol 2010; 45: 281-290
• 104 CF-Trust. Antibiotic treatment for cystic fibrosis: Report of the UK Cystic Fibrosis Trust Antibiotic Working Group. CF-Trust; 2009. Third edition
• 105 Latzin P, Fehling M, Bauernfeind A. et al. Efficacy and safety of intravenous meropenem and tobramycin versus ceftazidime and tobramycin in cystic fibrosis. J Cyst Fibros 2008; 7: 142-146
• 106 Emerson J, Rosenfeld M, McNamara S. et al. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol 2002; 34: 91-100
• 107 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 2001; 139: 572-577
• 108 Hennig S, McKay K, Vidmar S. et al. Safety of inhaled (Tobi(R)) and intravenous tobramycin in young children with cystic fibrosis. J Cyst Fibros 2014; 13: 428-434
• 109 Wang X, Koehne-Voss S, Anumolu SS. et al. Population Pharmacokinetics of Tobramycin Inhalation Solution in Pediatric Patients With Cystic Fibrosis. J Pharm Sci 2017; 106: 3402-3409
• 110 Heijerman H, Westerman E, Conway S. et al. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus. J Cyst Fibros 2009; 8: 295-315
• 111 Jain K, Wainwright C, Smyth AR. Bronchoscopy-guided antimicrobial therapy for cystic fibrosis. Cochrane Database Syst Rev 2018; 9: CD009530
• 112 Ronchetti K, Tame JD, Paisey C. et al. The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial. Lancet Respir Med 2018; 6: 461-471
• 113 Hansen CR, Pressler T, Hoiby N. Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience. J Cyst Fibros 2008; 7: 523-530
• 114 Blanchard AC, Horton E, Stanojevic S. et al. Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis. J Cyst Fibros 2017; 16: 395-400
• 115 Mogayzel Jr PJ, Naureckas ET, Robinson KA. et al. Cystic Fibrosis Foundation pulmonary guideline. pharmacologic approaches to prevention and eradication of initial Pseudomonas aeruginosa infection. Ann Am Thorac Soc 2014; 11: 1640-1650
• 116 Littlewood KJ, Higashi K, Jansen JP. et al. A network meta-analysis of the efficacy of inhaled antibiotics for chronic Pseudomonas infections in cystic fibrosis. J Cyst Fibros 2012; 11: 419-426
• 117 Geller DE, Konstan MW, Smith J. et al. Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. Pediatr Pulmonol 2007; 42: 307-313
• 118 Chuchalin A, Csiszer E, Gyurkovics K. et al. A formulation of aerosolized tobramycin (Bramitob) in the treatment of patients with cystic fibrosis and Pseudomonas aeruginosa infection: a double-blind, placebo-controlled, multicenter study. Paediatr Drugs 2007; 9 (Suppl. 01) 21-31
• 119 Clancy JP, Dupont L, Konstan MW. et al. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax 2013; 68: 818-825
• 120 Page MG, Dantier C, Desarbre E. In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant gram-negative bacilli. Antimicrob Agents Chemother 2010; 54: 2291-2302
• 121 Konstan MW, Flume PA, Kappler M. et al. Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cyst Fibros 2011; 10: 54-61
• 122 Schuster A, Haliburn C, Doring G. et al. Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study. Thorax 2013; 68: 344-350
• 123 Taccetti G, Campana S, Neri AS. et al. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis. J Chemother 2008; 20: 166-169
• 124 Edenborough FP, Borgo G, Knoop C. et al. Guidelines for the management of pregnancy in women with cystic fibrosis. J Cyst Fibros 2008; 7 (Suppl. 01) S2-S32
• 125 Kroon M, Akkerman-Nijland AM, Rottier BL. et al. Drugs during pregnancy and breast feeding in women diagnosed with Cystic Fibrosis – An update. J Cyst Fibros 2018; 17: 17-25
• 126 Remmington T, Jahnke N, Harkensee C. Oral anti-pseudomonal antibiotics for cystic fibrosis. Cochrane Database Syst Rev 2016; 7: CD005405
• 127 VanDevanter EJ, Heltshe SL, Skalland M. et al. The effect of oral and intravenous antimicrobials on pulmonary exacerbation recovery in cystic fibrosis. J Cyst Fibros 2021; 20: 932-936
• 128 Langan KM, Kotsimbos T, Peleg AY. Managing Pseudomonas aeruginosa respiratory infections in cystic fibrosis. Curr Opin Infect Dis 2015; 28: 547-556
• 129 Smyth A, Elborn JS. Exacerbations in cystic fibrosis: 3 – Management. Thorax 2008; 63: 180-184
• 130 Chmiel JF, Aksamit TR, Chotirmall SH. et al. Antibiotic management of lung infections in cystic fibrosis. I. The microbiome, methicillin-resistant Staphylococcus aureus, gram-negative bacteria, and multiple infections. Ann Am Thorac Soc 2014; 11: 1120-1129
• 131 Bell SC, Elborn JS, Byrnes CA. Bronchiectasis: Treatment decisions for pulmonary exacerbations and their prevention. Respirology (Carlton, Vic) 2018; 23: 1006-1022
• 132 Mayer-Hamblett N, Kronmal RA, Gibson RL. et al. Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis. Pediatr Pulmonol 2012; 47: 125-134
• 133 Smyth AR, Bhatt J. Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev 2014; 2: CD002009
• 134 Riethmueller J, Junge S, Schroeter TW. et al. Continuous vs thrice-daily ceftazidime for elective intravenous antipseudomonal therapy in cystic fibrosis. Infection 2009; 37: 418-423
• 135 Flume PA, Robinson KA, O'Sullivan BP. et al. Cystic fibrosis pulmonary guidelines: airway clearance therapies. Respir Care 2009; 54: 522-537
• 136 Elphick HE, Jahnke N. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis. Cochrane Database Syst Rev 2014; CD002007
• 137 Elphick HE, Scott A. Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis. Cochrane Database Syst Rev 2016; 12: CD002007
• 138 Blumer JL, Saiman L, Konstan MW. et al. The efficacy and safety of meropenem and tobramycin vs ceftazidime and tobramycin in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis. Chest 2005; 128: 2336-2346
• 139 Hubert D, Le Roux E, Lavrut T. et al. Continuous versus intermittent infusions of ceftazidime for treating exacerbation of cystic fibrosis. Antimicrob Agents Chemother 2009; 53: 3650-3656
• 140 Madsen V, Lind A, Rasmussen M. et al. Determination of tobramycin in saliva is not suitable for therapeutic drug monitoring of patients with cystic fibrosis. J Cyst Fibros 2004; 3: 249-251
• 141 Parkins MD, Rendall JC, Elborn JS. Incidence and risk factors for pulmonary exacerbation treatment failures in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa. Chest 2012; 141: 485-493
• 142 Sanders DB, Bittner RC, Rosenfeld M. et al. Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med 2010; 182: 627-632
• 143 Keays T, Ferris W, Vandemheen KL. et al. A retrospective analysis of biofilm antibiotic susceptibility testing: a better predictor of clinical response in cystic fibrosis exacerbations. J Cyst Fibros 2009; 8: 122-127
• 144 Tascini C, Gemignani G, Ferranti S. et al. Microbiological activity and clinical efficacy of a colistin and rifampin combination in multidrug-resistant Pseudomonas aeruginosa infections. J Chemother 2004; 16: 282-287
• 145 Falagas ME, Kastoris AC, Karageorgopoulos DE. et al. Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies. Int J Antimicrob Agents 2009; 34: 111-120
• 146 Mikuniya T, Kato Y, Kariyama R. et al. Synergistic effect of fosfomycin and fluoroquinolones against Pseudomonas aeruginosa growing in a biofilm. Acta medica Okayama 2005; 59: 209-216
• 147 McCaughey G, McKevitt M, Elborn JS. et al. Antimicrobial activity of fosfomycin and tobramycin in combination against cystic fibrosis pathogens under aerobic and anaerobic conditions. J Cyst Fibros 2012; 11: 163-172
• 148 Roehmel JF, Schwarz C, Mehl A. et al. Hypersensitivity to antibiotics in patients with cystic fibrosis. J Cyst Fibros 2014; 13: 205-211
• 149 Burrows JA, Nissen LM, Kirkpatrick CM. et al. Beta-lactam allergy in adults with cystic fibrosis. J Cyst Fibros 2007; 6: 297-303
• 150 Legere 3rd HJ, Palis RI, Rodriguez BouzaT. et al. A safe protocol for rapid desensitization in patients with cystic fibrosis and antibiotic hypersensitivity. J Cyst Fibros 2009; 8: 418-424
• 151 Whitaker P, Shaw N, Gooi J. et al. Rapid desensitization for non-immediate reactions in patients with cystic fibrosis. J Cyst Fibros 2011; 10: 282-285
• 152 Southern KW, Barker PM, Solis-Moya A. et al. Macrolide antibiotics for cystic fibrosis. Cochrane Database Syst Rev 2012; 11: CD002203
• 153 Nick JA, Moskowitz SM, Chmiel JF. et al. Azithromycin may antagonize inhaled tobramycin when targeting Pseudomonas aeruginosa in cystic fibrosis. Ann Am Thorac Soc 2014; 11: 342-350
• 154 VanDevanter DR, OʼRiordan MA, Blumer JL. et al. Assessing time to pulmonary function benefit following antibiotic treatment of acute cystic fibrosis exacerbations. Respir Res 2010; 11: 137
• 155 Adeboyeku D, Jones AL, Hodson ME. Twice vs three-times daily antibiotics in the treatment of pulmonary exacerbations of cystic fibrosis. J Cyst Fibros 2011; 10: 25-30
• 156 Smyth A, Tan KH, Hyman-Taylor P. et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis – the TOPIC study: a randomised controlled trial. Lancet 2005; 365: 573-578
• 157 Thornton J, Elliott RA, Tully MP. et al. Clinical and economic choices in the treatment of respiratory infections in cystic fibrosis: comparing hospital and home care. J Cyst Fibros 2005; 4: 239-247
• 158 Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev 2009; CD001506
• 159 Dentice R, Elkins M. Timing of dornase alfa inhalation for cystic fibrosis. Cochrane Database Syst Rev 2011; CD007923
• 160 Bradley J, Moran F. Physical training for cystic fibrosis. Cochrane Database Syst Rev 2008; CD002768
• 161 Bott J, Blumenthal S, Buxton M. et al. Guidelines for the physiotherapy management of the adult, medical, spontaneously breathing patient. Thorax 2009; 64 (Suppl. 01) i1-i51
• 162 Elkins MR, Robinson M, Rose BR. et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006; 354: 229-240
• 163 Elkins M, Dentice R. Timing of hypertonic saline inhalation for cystic fibrosis. Cochrane Database Syst Rev 2020; 2: CD008816
• 164 Fuchs HJ, Borowitz DS, Christiansen DH. et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med 1994; 331: 637-642
• 165 Conrad C, Lymp J, Thompson V. et al. Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial. J Cyst Fibros 2015; 14: 219-227
• 166 Stafanger G, Koch C. N-acetylcysteine in cystic fibrosis and Pseudomonas aeruginosa infection: clinical score, spirometry and ciliary motility. Eur Respir J 1989; 2: 234-237
• 167 Duijvestijn YC, Brand PL. Systematic review of N-acetylcysteine in cystic fibrosis. Acta Paediatr 1999; 88: 38-41
• 168 Ciofu O, Smith S, Lykkesfeldt J. Antioxidant supplementation for lung disease in cystic fibrosis. Cochrane Database Syst Rev 2019; 10: CD007020
• 169 Calverley P, Rogliani P, Papi A. Safety of N-Acetylcysteine at High Doses in Chronic Respiratory Diseases: A Review. Drug safety: an international journal of medical toxicology and drug experience 2021; 44: 273-290
• 170 Balfour-Lynn IM, Welch K, Smith S. Inhaled corticosteroids for cystic fibrosis. Cochrane Database Syst Rev 2019; 7: CD001915
• 171 Balfour-Lynn IM, Lees B, Hall P. et al. Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Am J Respir Crit Care Med 2006; 173: 1356-1362
• 172 Cheng K, Ashby D, Smyth RL. Oral steroids for long-term use in cystic fibrosis. Cochrane Database Syst Rev 2013; 6: CD000407
• 173 Lands LC, Stanojevic S. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis. Cochrane Database Syst Rev 2019; 9: CD001505
• 174 Halfhide C, Evans HJ, Couriel J. Inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev 2005; CD003428
• 175 Valverde-Molina J, Sanchez-Solis M, Pastor-Vivero MD. et al. [Association between chronic colonization or infection with Pseudomonas aeruginosa and bronchial hyperreactivity in patients with cystic fibrosis]. Archivos de bronconeumologia 2008; 44: 180-184
• 176 Boulet LP, Turcotte H, Tennina S. Comparative efficacy of salbutamol, ipratropium, and cromoglycate in the prevention of bronchospasm induced by exercise and hyperosmolar challenges. J Allergy Clin Immunol 1989; 83: 882-887
• 177 Vazquez C, Fidalgo I, Virto MC. et al. [Effectiveness of disodium cromoglycate, salbutamol, and ipratropium bromide in the inhibition of exercise-induced bronchospasm]. Anales espanoles de pediatria 1984; 20: 756-762
• 178 Mogayzel PJ Jr, Naureckas ET, Robinson KA. et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med 2013; 187: 680-689
• 179 Smith S, Edwards CT. Long-acting inhaled bronchodilators for cystic fibrosis. Cochrane Database Syst Rev 2017; 12: CD012102
• 180 Cai Y, Chai D, Wang R. et al. Effectiveness and safety of macrolides in cystic fibrosis patients: a meta-analysis and systematic review. J Antimicrob Chemother 2011; 66: 968-978
• 181 Nichols DP, Odem-Davis K, Cogen JD. et al. Pulmonary Outcomes Associated with Long-Term Azithromycin Therapy in Cystic Fibrosis. Am J Respir Crit Care Med 2020; 201: 430-437
• 182 Steinkamp G, Schmitt-Grohe S, Doring G. et al. Once-weekly azithromycin in cystic fibrosis with chronic Pseudomonas aeruginosa infection. Respir Med 2008; 102: 1643-1653
• 183 Kabra SK, Pawaiya R, Lodha R. et al. Long-term daily high and low doses of azithromycin in children with cystic fibrosis: a randomized controlled trial. J Cyst Fibros 2010; 9: 17-23
• 184 Renna M, Schaffner C, Brown K. et al. Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection. J Clin Invest 2011; 121: 3554-3563
• 185 Wozniak DJ, Keyser R. Effects of subinhibitory concentrations of macrolide antibiotics on Pseudomonas aeruginosa. Chest 2004; 125: 62S-69S quiz 9S
• 186 Ray WA, Murray KT, Hall K. et al. Azithromycin and the risk of cardiovascular death. N Engl J Med 2012; 366: 1881-1890
• 187 Akkerman-Nijland AM, Mohlmann JE, Akkerman OW. et al. The long-term safety of chronic azithromycin use in adult patients with cystic fibrosis, evaluating biomarkers for renal function, hepatic function and electrical properties of the heart. Expert Opin Drug Saf 2021; 20: 959-963
• 188 del Campo R, Garriga M, Perez-Aragon A. et al. Improvement of digestive health and reduction in proteobacterial populations in the gut microbiota of cystic fibrosis patients using a Lactobacillus reuteri probiotic preparation: a double blind prospective study. J Cyst Fibros 2014; 13: 716-722
• 189 Hebestreit H, Kieser S, Junge S. et al. Long-term effects of a partially supervised conditioning programme in cystic fibrosis. Eur Respir J 2010; 35: 578-583
• 190 Kriemler S, Kieser S, Junge S. et al. Effect of supervised training on FEV1 in cystic fibrosis: a randomised controlled trial. J Cyst Fibros 2013; 12: 714-720
• 191 Radtke T, Nevitt SJ, Hebestreit H. et al. Physical exercise training for cystic fibrosis. Cochrane Database Syst Rev 2017; 11: CD002768
• 192 Gruber W, Orenstein DM, Braumann KM. et al. Health-related fitness and trainability in children with cystic fibrosis. Pediatr Pulmonol 2008; 43: 953-964
• 193 Griese M, Busch P, Caroli D. et al. Rehabilitation Programs for Cystic Fibrosis – View from a CF Center. Open Respir Med J 2010; 4: 1-8
• 194 Quittner AL, Abbott J, Georgiopoulos AM. et al. International Committee on Mental Health in Cystic Fibrosis: Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus statements for screening and treating depression and anxiety. Thorax 2016; 71: 26-34
• 195 Hurley MN, Forrester DL, Smyth AR. Antibiotic adjuvant therapy for pulmonary infection in cystic fibrosis. Cochrane Database Syst Rev 2013; 6: CD008037
• 196 Boutin S, Graeber SY, Weitnauer M. et al. Comparison of microbiomes from different niches of upper and lower airways in children and adolescents with cystic fibrosis. PLoS One 2015; 10: e0116029
• 197 Aanaes K, Alanin MC, Nielsen KG. et al. The accessibility of topical treatment in the paranasal sinuses on operated cystic fibrosis patients assessed by scintigraphy. Rhinology 2018; 56: 268-273
• 198 Mainz JG, Michl R, Pfister W. et al. Cystic fibrosis upper airways primary colonization with Pseudomonas aeruginosa: eradicated by sinonasal antibiotic inhalation. Am J Respir Crit Care Med 2011; 184: 1089-1090
• 199 Mainz JGT, Lehmann C, Schien D. et al. 82 The upper airway role in acquisition of Pseudomonas aeruginosa colonization in cystic fibrosis patients. Longitudinal single centre analysis following 153 CF patients for up to 10.6 years. Journal of Cystic Fibrosis 2016; 15 (Suppl. 01) S72
• 200 Johansen HK, Aanaes K, Pressler T. et al. Colonisation and infection of the paranasal sinuses in cystic fibrosis patients is accompanied by a reduced PMN response. J Cyst Fibros 2012; 11: 525-531
• 201 Hansen SK, Rau MH, Johansen HK. et al. Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection. ISME J 2011; 6: 31-45
• 202 Mainz JG, Hentschel J, Schien C. et al. Sinonasal persistence of Pseudomonas aeruginosa after lung transplantation. J Cyst Fibros 2012; 11: 158-161
• 203 Morlacchi LC, Greer M, Tudorache I. et al. The burden of sinus disease in cystic fibrosis lung transplant recipients. Transpl Infect Dis 2018; 20: e12924
• 204 Mainz JG, Gerber A, Lorenz M. et al. Pseudomonas aeruginosa Acquisition in Cystic Fibrosis Patients in Context of Otorhinolaryngological Surgery or Dentist Attendance: Case Series and Discussion of Preventive Concepts. Case Rep Infect Dis 2015; 2015: 438517
• 205 Mainz JG, Baier M, Jaudszus A. et al. Pseudomonas aeruginosa colonization in the upper and lower airways of a child with cystic fibrosis: a father's meticulous approach to successful eradication. J Bras Pneumol 2019; 45: e20190191
• 206 Hentschel J, Muller U, Doht F. et al. Influences of nasal lavage collection-, processing- and storage methods on inflammatory markers – evaluation of a method for non-invasive sampling of epithelial lining fluid in cystic fibrosis and other respiratory diseases. JJ Immunol Methods 2014; 404: 41-51
• 207 Hentschel J, Wullenkord T, Schilling WK. et al. 44 Upper airway sampling in preschool CF patients to assess pathogen colonization and inflammation. J Cyst Fibros 2016; 15 (Suppl. 01) S62
• 208 Koitschev A, Wolff A, Koitschev C. et al. Standardisierte HNO-Untersuchung bei Patienten mit Mukoviszidose. HNO 2006; 5. https://www.springermedizin.de/de/standardisierte-hno-untersuchung-bei-patienten-mit-mukoviszidose/8031646
• 209 Doht F, Hentschel J, Fischer N. et al. Reduced effect of intravenous antibiotic treatment on sinonasal markers in pulmonary inflammation. Rhinology 2015; 53: 249-259
• 210 Moller W, Saba GK, Haussinger K. et al. Nasally inhaled pulsating aerosols: lung, sinus and nose deposition. Rhinology 2011; 49: 286-291
• 211 Davidson TM, Murphy C, Mitchell M. et al. Management of chronic sinusitis in cystic fibrosis. The Laryngoscope 1995; 105: 354-358
• 212 Aanaes K. Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis. J Cyst Fibros 2013; 12 (Suppl. 02) S1-S20
• 213 Möller W, Schuschnig U, Khadem Saba G. et al. Pulsating aerosols for drug delivery to the sinuses in healthy volunteers. Otolaryngol Head Neck Surg 2010; 142: 382-388
• 214 Mainz JG, Schien C, Schädlich K. et al. Sinonasal inhalation of Tobramycin in CF-patients with P. aeruginosa-colonization of the upper airways – results of a multicentric placebo controlled pilot study. J Cyst Fibros 2011; 10S: 21
• 215 Mainz JG, Schadlich K, Schien C. et al. Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double-blind, placebo-controlled pilot study. Drug Des Devel Ther 2014; 8: 209-217
• 216 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 2004; 23: 93-97
• 217 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 2006; 61: 80-85
• 218 Wielputz MO, Puderbach M, Kopp-Schneider A. et al. Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med 2014; 189: 956-965
• 219 Sly PD, Gangell CL, Chen L. et al. Risk factors for bronchiectasis in children with cystic fibrosis. N Engl J Med 2013; 368: 1963-1970
• 220 Peixoto AO, Marson FAL, Souza TH. et al. Lung ultrasound assessment of response to antibiotic therapy in cystic fibrosis exacerbations: a study of two cases. J Bras Pneumol 2019; 45: e20190128
• 221 Larke FJ, Kruger RL, Cagnon CH. et al. Estimated radiation dose associated with low-dose chest CT of average-size participants in the National Lung Screening Trial. AJR Am J Roentgenol 2011; 197: 1165-1169
• 222 Kuo W, Kemner-van de Corput MP, Perez-Rovira A. et al. Multicentre chest computed tomography standardisation in children and adolescents with cystic fibrosis: the way forward. Eur Respir J 2016; 47: 1706-1717
• 223 Berkhout MC, Rijntjes E, El Bouazzaoui LH. et al. Importance of bacteriology in upper airways of patients with Cystic Fibrosis. J Cyst Fibros 2013; 12: 525-529
• 224 Eggesbo HB, Sovik S, Dolvik S. et al. Proposal of a CT scoring system of the paranasal sinuses in diagnosing cystic fibrosis. Eur Radiol 2003; 13: 1451-1460
• 225 Sommerburg O, Wielputz MO, Trame JP. et al. Magnetic Resonance Imaging Detects Chronic Rhinosinusitis in Infants and Preschool Children with Cystic Fibrosis. Ann Am Thorac Soc 2020; 17: 714-723
• 226 Farrell PM, Collins J, Broderick LS. et al. Association between mucoid Pseudomonas infection and bronchiectasis in children with cystic fibrosis. Radiology 2009; 252: 534-543
• 227 Loeve M, Gerbrands K, Hop WC. et al. Bronchiectasis and pulmonary exacerbations in children and young adults with cystic fibrosis. Chest 2011; 140: 178-185
• 228 Rosenfeld M, Ratjen F, Brumback L. et al. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA 2012; 307: 2269-2277
• 229 Nasr SZ, Sakmar E, Christodoulou E. et al. The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease. Pediatr Pulmonol 2010; 45: 440-449
• 230 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 2007; 175: 943-950
• 231 Berkhout MC, Klerx-Melis F, Fokkens WJ. et al. CT-abnormalities, bacteriology and symptoms of sinonasal disease in children with Cystic Fibrosis. J Cyst Fibros 2016; 15: 816-824
• 232 Ball R, Southern KW, McCormack P. et al. Adherence to nebulised therapies in adolescents with cystic fibrosis is best on week-days during school term-time. J Cyst Fibros 2013; 12: 440-444
• 233 George M, Rand-Giovannetti D, Eakin MN. et al. Perceptions of barriers and facilitators: self-management decisions by older adolescents and adults with CF. J Cyst Fibros 2010; 9: 425-432
• 234 Modi AC, Quittner AL. Barriers to treatment adherence for children with cystic fibrosis and asthma: what gets in the way?. J Pediatr Psychol 2006; 31: 846-858
• 235 Quittner AL, Zhang J, Marynchenko M. et al. Pulmonary medication adherence and health-care use in cystic fibrosis. Chest 2014; 146: 142-151
• 236 Eakin MN, Bilderback A, Boyle MP. et al. Longitudinal association between medication adherence and lung health in people with cystic fibrosis. J Cyst Fibros 2011; 10: 258-264
• 237 Sawicki GS, Signorovitch JE, Zhang J. et al. Reduced mortality in cystic fibrosis patients treated with tobramycin inhalation solution. Pediatr Pulmonol 2012; 47: 44-52
• 238 Dibonaventura M, Gabriel S, Dupclay L. et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry 2012; 12: 20