Dina Visca1, Letizia Mori2, Vicky Tsipouri2, Sharon Fleming3, Ashi Firouzi3, Matteo Bonini3, Matthew J Pavitt3, Veronica Alfieri4, Sara Canu5, Martina Bonifazi6, Cristina Boccabella7, Angelo De Lauretis8, Carmel J W Stock9, Peter Saunders9, Andrew Montgomery10, Charlotte Hogben11, Anna Stockford12, Margaux Pittet12, Jo Brown13, Felix Chua2, Peter M George2, Philip L Molyneaux14, Georgios A Margaritopoulos11, Maria Kokosi11, Vasileios Kouranos11, Anne Marie Russell15, Surinder S Birring16, Alfredo Chetta17, Toby M Maher9, Paul Cullinan18, Nicholas S Hopkinson3, Winston Banya19, Jennifer A Whitty20, Huzaifa Adamali12, Lisa G Spencer13, Morag Farquhar21, Piersante Sestini22, Athol U Wells9, Elisabetta A Renzoni23. 1. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Division of Pulmonary Rehabilitation, Istituti Clinici Scientifici Maugeri, IRCCS, Tradate, Italy. 2. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; NIHR Clinical Research Facility, Royal Brompton Hospital, London, UK. 3. NIHR Clinical Research Facility, Royal Brompton Hospital, London, UK. 4. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy. 5. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Lung Disease Unit, Department of Clinical and Experimental Medicine, University of Sassari, Italy. 6. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Department of Biomedical Sciences and Public Health, Universita' Politecnica delle Marche, Ancona, Italy. 7. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Unita Operativa Complessa di Pneumologia, Universita' Cattolica del Sacro Cuore, Rome, Italy. 8. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Unita' Operativa Malattie Respiratorie, Ospedale Guido Salvini, Garbagnate Milanese, Milan, Italy. 9. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; NIHR Clinical Research Facility, Royal Brompton Hospital, London, UK; Fibrosis Research Group, Inflammation Repair and Development Section, Imperial College, London, UK. 10. Rehabilitation and Therapies, Royal Brompton Hospital, London, UK. 11. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK. 12. Bristol Interstitial Lung Disease Service, Southmead Hospital, Bristol, UK. 13. Aintree Chest Centre, University Hospital Aintree, Liverpool, UK. 14. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; Fibrosis Research Group, Inflammation Repair and Development Section, Imperial College, London, UK. 15. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; National Heart and Lung Institute, Imperial College, London, UK. 16. Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK. 17. Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy. 18. National Heart and Lung Institute, Imperial College, London, UK. 19. NIHR Clinical Research Facility, Royal Brompton Hospital, London, UK; National Heart and Lung Institute, Imperial College, London, UK. 20. Health Economics Group, Norwich Medical School, University of East Anglia, Norwich, UK. 21. School of Health Sciences, University of East Anglia, Norwich, UK. 22. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. 23. Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK; NIHR Clinical Research Facility, Royal Brompton Hospital, London, UK; Fibrosis Research Group, Inflammation Repair and Development Section, Imperial College, London, UK. Electronic address: e.renzoni@rbht.nhs.uk.
Abstract
BACKGROUND: In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS: AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS: Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. INTERPRETATION:Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. FUNDING: UK National Institute for Health Research.
RCT Entities:
BACKGROUND: In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS: AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS: Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. INTERPRETATION: Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. FUNDING: UK National Institute for Health Research.
Authors: Anna-Maria Hoffmann-Vold; Yannick Allanore; Elisabeth Bendstrup; Cosimo Bruni; Oliver Distler; Toby M Maher; Marlies Wijsenbeek; Michael Kreuter Journal: Respir Res Date: 2020-07-23
Authors: Paola Faverio; Federica De Giacomi; Giulia Bonaiti; Anna Stainer; Luca Sardella; Giulia Pellegrino; Giuseppe Francesco Sferrazza Papa; Francesco Bini; Bruno Dino Bodini; Mauro Carone; Sara Annoni; Grazia Messinesi; Alberto Pesci Journal: Int J Med Sci Date: 2019-06-10 Impact factor: 3.738