The Italian REgistry of Pulmonary Non-tuberculous mycobactEria

The epidemiology of patients suffering from a pulmonary disease due to NTM (NTM-PD), which is characterized by symptomatic, progressive inflammatory lung damage and defined in 2007 in the ATS/IDSA guidelines, still remains unclear. Reporting of NTM-PD to health authorities is often not mandated in several countries and the current estimates have been obtained from sentinel surveillance or laboratory-based studies, retrospective cohort studies, or audits of administrative databases. Until now no data have been published on the epidemiology of respiratory NTM infections in Italy.

The Italian registry of pulmonary NTM (IRENE) is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory infection or NTM-PD. The coordinating center is located at the Pulmonary Department of the Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. So far, more than 35 centers, including mainly pulmonary and infectious disease departments, joined the registry. The study is sponsored by the Policlinico Hospital in Milan. The study website is located at www.registroirene.it.

Adult (>=18 years) patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) Given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients included in the registry are mainly recruited among pulmonary and ID out- and in-patient services. Adult cystic fibrosis, lung transplant, and tuberculosis clinics represent other recruitment centers. The registry has been developed to accept an unlimited number of patients and no deadlines have been decided.

Patients are managed according to standard operating procedures implemented in each IRENE clinical center without any interference from the study team. A baseline case report form is collected at patient's enrolment including demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, and treatment data. Then, study investigators enter follow-up data on an annual basis.

An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. IRENE sites can collect samples, including blood, serum, plasma, respiratory specimens (sputum, induced sputum, tracheal aspirate, or bronchoalveolar lavage), urine, and NTM isolates at the first visit and during follow up on a voluntary basis.

Primary outcomes

• Proportion of patients meeting the quality standards for NTM-PD care suggested by international guidelines (including the latest ERS 2017 guidelines) [5 years]: The number of patients with NTM-PD who have been managed or treated according to the recommendations published by international guidelines

Sex: All, ages: 18 Years to any

Inclusion Criteria (all of them):

* Adult (>=18 years) patients
* At least one positive culture for any NTM species from any respiratory sample
* At least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrollment
* Given consent to inclusion in the study.

Exclusion Criteria:

No exclusion criteria are applied to the study

• Haworth CS, Banks J, Capstick T, Fisher AJ, Gorsuch T, Laurenson IF, Leitch A, Loebinger MR, Milburn HJ, Nightingale M, Ormerod P, Shingadia D, Smith D, Whitehead N, Wilson R, Floto RA. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017 Nov;72(Suppl 2):ii1-ii64. doi: 10.1136/thoraxjnl-2017-210927. No abstract available. PMID 29054853
• Faverio P, Stainer A, Bonaiti G, Zucchetti SC, Simonetta E, Lapadula G, Marruchella A, Gori A, Blasi F, Codecasa L, Pesci A, Chalmers JD, Loebinger MR, Aliberti S. Characterizing Non-Tuberculous Mycobacteria Infection in Bronchiectasis. Int J Mol Sci. 2016 Nov 16;17(11):1913. doi: 10.3390/ijms17111913. PMID 27854334
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• Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ Jr, Winthrop K; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416. doi: 10.1164/rccm.200604-571ST. No abstract available. PMID 17277290
• Floto RA, Olivier KN, Saiman L, Daley CL, Herrmann JL, Nick JA, Noone PG, Bilton D, Corris P, Gibson RL, Hempstead SE, Koetz K, Sabadosa KA, Sermet-Gaudelus I, Smyth AR, van Ingen J, Wallace RJ, Winthrop KL, Marshall BC, Haworth CS; US Cystic Fibrosis Foundation and European Cystic Fibrosis Society. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax. 2016 Jan;71 Suppl 1(Suppl 1):i1-22. doi: 10.1136/thoraxjnl-2015-207360. PMID 26666259
• Results publication: Aliberti S, Codecasa LR, Gori A, Sotgiu G, Spotti M, Di Biagio A, Calcagno A, Nardini S, Assael BM, Tortoli E, Besozzi G, Ferrarese M, Matteelli A, Girardi E, De Lorenzo S, Seia M, Gramegna A, Del Prato B, Terranova L, Oriano M, Sverzellati N, Mirsaeidi M, Chalmers JD, Haworth CS, Loebinger MR, Aksamit T, Winthrop K, Ringshausen FC, Previdi G, Blasi F; IRENE Network. The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE: the study protocol. Multidiscip Respir Med. 2018 Aug 9;13(Suppl 1):33. doi: 10.1186/s40248-018-0141-8. eCollection 2018. PMID 30151192

• Study Protocol (PDF, 2017-06-21)
• Statistical Analysis Plan (PDF, 2017-06-21)

• Stefano Aliberti, MD, Study director, Department of Pathophysiology and Transplantation, University of Milan Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
• Francesco Blasi, MD, Study chair, Department of Pathophysiology and Transplantation, University of Milan Internal Medicine Department, Respiratory Unit and Cystic Fibrosis Adult Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
• Luigi Ruffo Codecasa, MD, Study chair, Regional TB Reference Centre, Istituto Villa Marelli, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
• Andrea Gori, MD, Study chair, Clinic of Infectious Diseases, 'San Gerardo" Hospital-ASST Monza, University Milano-Bicocca, Milano, Italy