The Italian Registry of Pulmonary Non-tuberculous Mycobacteria
Conditions: Nontuberculous Mycobacteria
Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
STUDY PROTOCOL 
The Italian REgistry of pulmonary Non-tuberculous mycobactEria – IRENE 
Version #:  
 
            2.0 
Date:  
 
 
June 21st, 2017 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
Study Sponsor:  
UO di Broncopneumologia, Dipar6mento delle Units mul6specialis6che e dei trapian6 / Area 
Cardio-Polmonare, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano 
Principal Inves,gator:  
 

Prof. Stefano Aliber6, Dipar6mento di Fisiopatologia Medico-Chirurgica e dei Trapian6, 
Università degli Studi di Milano, UO di Broncopneumologia, Dipar6mento delle Units 
mul6specialis6che e dei trapian6 / Area Cardio-Polmonare, Fondazione IRCCS Ca’ Granda 
Ospedale Maggiore Policlinico, Milano; E-mail: stefano.aliber6@unimi.it. 
Execu,ve commi.ee:

Prof. Stefano Aliber6, Dipar6mento di Fisiopatologia Medico-Chirurgica e dei Trapian6, 
Università degli Studi di Milano, UO di Broncopneumologia, Dipar6mento delle Units 
mul6specialis6che e dei trapian6 / Area Cardio-Polmonare, Fondazione IRCCS Ca’ Granda 
Ospedale Maggiore Policlinico, Milano; E-mail: stefano.aliber6@unimi.it. 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it

Prof. Francesco Blasi, Dipar6mento di Fisiopatologia Medico-Chirurgica e dei Trapian6, 
Università degli Studi di Milano, UO di Broncopneumologia, Dipar6mento delle Units 
mul6specialis6che e dei trapian6 / Area Cardio-Polmonare, Fondazione IRCCS Ca’ Granda 
Ospedale Maggiore Policlinico, Milano; E-mail: francesco.blasi@unimi.it. 

Dr. Luigi Ruﬀo Codecasa, Centro regionale di riferimento per TB, Is6tuto Villa Marelli, ASST 
G r a n d e O s p e d a l e M e t r o p o l i t a n o N i g u a r d a , M i l a n o ; E - m a i l : 
luigiruﬀo.codecasa@ospedaleniguarda.it 

Prof. Andrea Gori, Scuola di Medicina e Chirurgia, Università degli Studi di Milano Bicocca, 
UO Mala9e Infe9ve, ASST di Monza, Ospedale San Gerardo, Monza; E-Mail: 
andrea.gori@unimib.it 
Scien,ﬁc Commi.ee
1. Prof. Stefano Aliber6, Dipar6mento di Fisiopatologia Medico-Chirurgica e dei Trapian6, 
Università degli Studi di Milano, UO di Broncopneumologia, Dipar6mento delle Units 
mul6specialis6che e dei trapian6 / Area Cardio-Polmonare, Fondazione IRCCS Ca’ Granda 
Ospedale Maggiore Policlinico, Milano 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
2. Prof. Francesco Blasi, Dipar6mento di Fisiopatologia Medico-Chirurgica e dei Trapian6, 
Università degli Studi di Milano, UO di Broncopneumologia, Dipar6mento delle Units 
mul6specialis6che e dei trapian6 / Area Cardio-Polmonare, Fondazione IRCCS Ca’ Granda 
Ospedale Maggiore Policlinico, Milano 
3. Dr. Luigi Ruﬀo Codecasa, Centro regionale di riferimento per TB, Is6tuto Villa Marelli, ASST 
Grande Ospedale Metropolitano Niguarda, Milano 
4. Prof. Andrea Gori, Scuola di Medicina e Chirurgia, Università degli Studi di Milano Bicocca, 
UO Mala9e Infe9ve, ASST di Monza, Ospedale San Gerardo, Monza 
5. Prof. Giovanni Sotgiu, Clinical Epidemiology and Medical Sta6s6cs Unit, Department of 
Biomedical Sciences, Università degli Studi di Sassari, Sassari, Italia  
6. Dr Stefano Nardini, UO di Pneumo6siologia, Ospedale  di Vi8orio Veneto, Treviso, Italia 
7. Dr Mehdi Mirsaeidi, Division of Pulmonary and Cri6cal Care, University of Miami, 1600 NW, 
Miami, FL 33136, USA; Miami VA Medical Center, 1201 N.W. 16th St., Miami, FL 33125, 
USA.  
8. Dr Enrico Tortoli, Emerging Bacterial Pathogens Unit, IRCCS Ospedale San Raﬀaele, Milano, 
Italia 
9. Dr Giorgio Besozzi, Stop TB Italia, Milano, Italia 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
10.  Dr Alberto Ma8eelli, Clinic of Infec6ous and Tropical Diseases, University of Brescia and 
Brescia Spedali Civili General Hospital, WHO Collabora6ng Centre for TB/HIV and TB 
Elimina6on, Brescia, Italia
11.  Dr Antonio Di Biagio, IRCCS-AOU-San Mar6no-IST, Infec6ous Disease Clinic, Genova, Italia
12. Dr Andrea Calcagno, Università degli Studi di Torino  
13. Dr Girardi Spallanzani, UOC Epidemiologia Clinica - Dipar6mento di Epidemiologia e Ricerca 
Preclinica, Clinical Epidemiology Unit - Department of Epidemiology and Preclinical 
Research Is6tuto Nazionale Mala9e Infe9ve "L. Spallanzani" – IRCCS Via Portuense 292, 
00149 Roma 
14. Dr Giuliana Previdi, rappresentate pazien6 
       15. Dr Baroukh Maurice Assael, Università degli Studi di Milano, UO di Broncopneumologia, 
Dipar6mento delle Units mul6specialis6che e dei trapian6 / Area Cardio-Polmonare, Fondazione 
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
BACKGROUND 
Pulmonary disease due to non-tuberculous mycobacteria (NTM) has always been a tangible clinical 
en6ty [1]. An increase in NTM pulmonary and extra-pulmonary morbidity and mortality has been 
documented in Italy and worldwide, especially among pa6ents suﬀering from chronic respiratory 
diseases, including bronchiectasis, chronic obstruc6ve pulmonary disease (COPD), or cys6c ﬁbrosis 
(CF), as well as among HIV-posi6ve and other immunocompromised pa6ents [2-11]. Several 
determinants of the increasing epidemiological trend have been iden6ﬁed: the aging of the 
popula6on with high prevalence of chronic and debilita6ng diseases; an intensiﬁed use of 
immunosuppressive therapies; a broader use of chest CT; a high diagnos6c yield of microbiological 
conven6onal and molecular techniques; an increasing environmental exposure to NTM; an 
increase use of an6bio6cs which can favor the occurrence of niches for NTM; declining rates of M. 
tuberculosis infec6on; and a poten6al impact of person-to-person transmission as recently 
suggested among CF pa6ents [12,13]. 
The epidemiology of pa6ents suﬀering from a pulmonary disease due to NTM (NTM-PD), which is 
characterized by symptoma6c, progressive inﬂammatory lung damage and deﬁned in 2007 in the 
ATS/IDSA guidelines, s6ll remains unclear [14,15]. Epidemiological and clinical uncertain6es on 
NTM-PD cause signiﬁcant confusion for clinicians in daily clinical prac6ce when asked to diagnose 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
NTM-PD. The clinical relevance of NTM respiratory infec6ons signiﬁcantly varies from pa6ent to 
pa6ent, and the interplay between exposure- and host-related factors is poorly understood [15]. 
NTM-PD shows a wide spectrum of clinical manifesta6ons and frequently is diagnosed in the 
context of concomitant respiratory diseases (e.g., bronchiectasis or CF) [3]. Geographical diversity 
is another important factor in the epidemiology of NTM. A large inter- and intra-country 
heterogeneity in distribu6on of NTM species has been recently shown [16,17]. Finally, an Italian 
experience described NTM-PD risk factors whose qualita6ve and quan6ta6ve ascertainment could 
help clinicians to discriminate between coloniza6on and disease [18]. 
Repor6ng of NTM-PD to health authori6es is o%en not mandated in several countries and the 
current es6mates have been obtained from sen6nel surveillance or laboratory-based studies, 
retrospec6ve cohort studies, or audits of administra6ve databases. Only a few European countries 
(i.e., UK, Greece, Germany, and the Netherlands) have provided epidemiological data, showing an 
incidence rate of NTM isola6on ranging from 2.9 to 7.0 per 100,000 popula6on and a NTM-PD 
prevalence of 0.7-1.7 per 100,000 popula6on [19-21]. Un6l now no data have been published on 
the epidemiology of respiratory NTM infec6ons in Italy. 
On this basis, robust na6onal longitudinal data are needed. This manuscript describes the protocol 
of the ﬁrst Italian registry of adult pa6ents with respiratory infec6ons caused by NTM.  

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
METHODOLOGY OF THE IRENE REGISTRY 
Study design  
The Italian registry of pulmonary NTM (IRENE) is an observa6onal, mul6center, prospec6ve, cohort 
study enrolling consecu6ve adult pa6ents with either a NTM respiratory infec6on or NTM-PD. The 
coordina6ng center is located at the Pulmonary Department of the Fondazione IRCCS Ca’ Granda, 
Ospedale Maggiore Policlinico (hereby referred to as Policlinico Hospital), Milan, Italy, where the 
central approval from the Ethical Commi8ee (EC) for this study was obtained on March 6th, 2017, 
and the ﬁrst pa6ent was enrolled on April 21st, 2017. A total of 35 centers, including mainly 
pulmonary and infec6ous disease (ID) departments, requested to join the registry, see Figure 1. All 
the centers are required to obtain local EC approval before entering the registry. Addi6onally, other 
EC approvals will be required by IRENE centers prior to commencement of the study at each site. 
All pa6ents must provide wri8en informed consent to par6cipate in the registry. The study is 
sponsored by the Policlinico Hospital in Milan.  

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
Study subjects 
Adult (≥18 years) pa6ents with all of the following will be included in the registry: 1) at least one 
posi6ve culture for any NTM species from any respiratory sample; 2) at least one posi6ve 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 in order to increase the generalizability of the results. The inclusion criteria of the 
registry clearly iden6fy a popula6on of pa6ents characterized by a recent/ongoing history of either 
a NTM infec6on or NTM-PD. The IRENE Steering Commi8ee decided not to limit the enrolment to 
pa6ents with NTM-PD, but to follow up also pa6ents with a recent NTM infec6on not fulﬁlling the 
2007 ATS/IDSA criteria for NTM-PD [15]. 
Pa6ents included in the registry are mainly recruited among pulmonary and ID out- and in-pa6ent 
services. Adult CF, lung transplant, and tuberculosis clinics represent other recruitment centers. A 
heterogeneous popula6on of pa6ents with NTM infec6on/NTM-PD sharing diﬀerent clinical 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
phenotypes is expected to be enrolled in the registry. IRENE has a special focus on four pa6ents’ 
categories: 1) immunocompetent/bronchiecta6c, 2) HIV-posi6ve, 3) CF and 4) lung transplanted 
pa6ents. 500 pa6ents are expected to be enrolled in the registry by the end of 2020. The registry 
has been developed to accept an unlimited number of pa6ents and no deadlines have been 
decided. 
Data Collec,on, deﬁni,ons and quality control 
Pa6ents are managed according to standard opera6ng procedures (SOPs) implemented in each 
IRENE clinical center without any interference from the study team. A baseline case report form 
(CRF) is collected at pa6ent’s enrolment including demographics, comorbidi6es, microbiological, 
laboratory, func6onal, radiological, clinical, and treatment data. Then, study inves6gators will enter 
follow-up data on an annual basis, see online supplement. Furthermore, a “start treatment” and a 
“stop treatment” CRF will also be collected. The database incorporates automated logic checks put 
in place to avoid the collec6on of out-of-range values. Once the case is entered into the registry, 
two members of the study team (SA and MS) manually veriﬁed its consistency and data queries 
will be solved with the local study inves6gator. In case of unresolved queries or incomplete cases, 
they will be rejected to have high quality data. To assure the high quality of the data, random audit 
will also be conducted at study sites. 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
IRENE Biobank 
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 (e.g., sputum, induced sputum, tracheal aspirate, or bronchoalveolar lavage), urine, and 
NTM isolates at the ﬁrst visit and during follow up on a voluntary basis. The same SOPs for 
biological collec6on, processing, and storage (ﬁrst locally and then centralized at the Policlinico 
Hospital in Milan for analysis) will be adopted by all IRENE sites. 
The registry governance and the IRENE network 
The registry is held securely at the Health Informa6cs Centre (HIC) of the Policlinico Hospital in 
Milan, Italy, and de-iden6ﬁed data will be accessible to the study inves6gators; however, they can 
have unrestricted access to their own data. Analysis of the en6re IRENE database will be allowed 
a%er the submission of a speciﬁc research ques6on, along with a complete study protocol, to the 
IRENE Execu6ve Commi8ee. The database will be run in accordance with the principles of Good 
Clinical Prac6ce. Study results will be disseminated in the form of annual reports, conference 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
abstracts, and peer reviewed publica6ons. The IRENE network will follow the Interna6onal 
Commi8ee of Medical Journal Editors recommenda6ons regarding authorship. 
IRENE is the oﬃcial Italian network within the EMBARC European NTM registry [22]. All Italian 
pa6ents included in the European NTM registry will be enrolled through IRENE and IRENE data will 
be incorporated into the European NTM registry.  
IRENE also promotes mul6-disciplinary educa6on and pa6ent-professional collabora6on in the 
ﬁeld of NTM through its rela6onship with na6onal scien6ﬁc socie6es. So far, IRENE received the 
endorsement by the Italian Respiratory Society (IRS/SIP), the Italian Society of Cys6c ﬁbrosis and 
STOP TB Italia, with pending endorsement from other na6onal scien6ﬁc socie6es. There is a lack of 
a pla5orm for communica6on between pa6ents with NTM infec6on/NTM-PD and physicians in 
Italy and some pa6ents within the IRENE network already expressed their will to develop a pa6ent 
advisory group. 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
REFERENCES 
1. Piersimoni C, Scarparo C. Pulmonary infec6ons associated with non-tuberculous 
mycobacteria in immunocompetent pa6ents. Lancet Infect Dis. 2008 May;8(5):323-34  
2. Rindi L, Garzelli C. Increase in non-tuberculous mycobacteria isolated from humans in 
Tuscany, Italy, from 2004 to 2014. BMC Infect Dis. 2016 Feb 1;16:44 
3. Bonai6 G, Pesci A, Marruchella A, Lapadula G, Gori A, Aliber6 S. Nontuberculous 
Mycobacteria in Noncys6c Fibrosis Bronchiectasis. Biomed Res Int. 2015;2015:197950.
4. Faverio P, Stainer A, Bonai6 G, Zucche9 SC, Simone8a E, Lapadula G, Marruchella A, Gori A, 
Blasi F, Codecasa L, Pesci A, Chalmers JD, Loebinger MR, Aliber6 S. Characterizing Non-
Tuberculous Mycobacteria Infec6on in Bronchiectasis. Int J Mol Sci. 2016 Nov 16;17 
5. Kendall BA, Winthrop KL. Update on the epidemiology of pulmonary nontuberculous 
mycobacterial infec6ons. Semin Respir Crit Care Med 2013;34:87–94 
6. Prevots DR, Marras TK. Epidemiology of human pulmonary infec6on with nontuberculous 
mycobacteria: a review. Clinics in Chest medicine 2015; 36 (1): 13-34 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
7. van der Werf MJ, Ködmön C, Katalinić-Janković V, Kummik T, Soini H, Richter E, et al. 
Inventory study of non-tuberculous mycobacteria in the European Union. BMC Infect Dis. 
2014;14:62.  
8. Ringshausen FC, Apel RM, Bange FC, de Roux A, Pletz MW, Rademacher J, et al. Burden and 
trends of hospitalisa6ons associated with pulmonary non- tuberculous mycobacterial 
infec6ons in Germany, 2005–2011. BMC Infect Dis. 2013;13:231.  
9. Moore JE, Kruijshaar ME, Ormerod LP, Drobniewski F, Abubakar I. Increasing reports of non-
tuberculous mycobacteria in England, Wales and Northern Ireland, 1995–2006. BMC Public 
Health. 2010;10:612. 
10. Biondi G, Sotgiu G, Dore S, Molico9 P, Ruggeri M, Aliber6 S, Sa8a R. Beyond pulmonary 
nontuberculous mycobacteria disease: do extra-pulmonary forms represent an emerging 
clinical and public health threat? ERJ Open Res. 2017 Sep 19;3(3). pii: 00091-2017
11. Mirsaeidi M, Machado RF, Garcia JG, Schraufnagel DE. Nontuberculous mycobacterial 
disease mortality in the united states, 1999-2010: A popula6on-based compara6ve study. 
PLoS One 2014;9(3):e91879 
12. Brode SK, Daley CL, Marras TK. The epidemiologic rela6onship between tuberculosis and 
non-tuberculous mycobactyerial disease: a systema6c review. IJTLD 2014; 18 (11): 1370-7 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
13. Bryant CE; Grogono DM, Rodriguez-rincon D. Popula6on-level genomics iden6ﬁes the 
emergence and global spread of a human transmissible mul6drug-resistant 
nontuberculuous mycobacterium. Science 2016  
14. Diel R, Jacob J, Lampenius N, Loebinger M, Nienhaus A, Rabe KF, Ringshausen FC. Burden of 
non-tuberculous mycobacterial pulmonary disease in Germany. Eur Respir J. 2017 Apr 
26;49(4) 
15. Griﬃth DE, Aksamit T, Brown-Ellio8 BA, Catanzaro A, Daley C, Gordin F, Holland SM, 
Horsburgh R, Hui8 G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ 
Jr, Winthrop K; ATS Mycobacterial Diseases Subcommi8ee; American Thoracic Society; 
Infec6ous Disease Society of America. An oﬃcial ATS/IDSA statement: diagnosis, treatment, 
and preven6on of nontuberculous mycobacterial diseases. Am J Respir Crit Care 
Med. 2007 Feb 15;175(4):367-416. Review. No abstract available. Erratum in: Am J Respir 
Crit Care Med. 2007 Apr 1;175(7):744-5. 
16. Hoefsloot W, van Ingen J, Andrejak C, Angeby K, Bauriaud R, Bemer P, et al. The geographic 
diversity of nontuberculous mycobacteria isolated from pulmonary samples: an NTM-NET 
collabora6ve study. Eur Respir J 2013;42:1604–13 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
17. Mirsaeidi M, Vu A, Leitman P, Shariﬁ A, Wisliceny S, Leitman A, Schmid A, Campos M, 
Falkinham J, Salathe M. A pa6ent-based analysis of the geographic distribu6on of 
mycobacterium avium complex, mycobacterium abscessus, and mycobacterium kansasii 
infec6ons in the united states. Chest 2017;151(4):947-950 
18. Mencarini J, Cresci C, Simone9 MT, Truppa C, Camicio8oli G, Frilli ML, Rogasi PG, Veloci S, 
Pistolesi M, Rossolini GM, Bartoloni A, Bartalesi F. Non-tuberculous mycobacteria: 
epidemiological pa8ern in a reference laboratory and risk factors associated with 
pulmonary disease. Epidemiol Infect. 2017 Feb;145(3):515-522 
19. Henry MT, Inamdar L, O’Riordain D, Schweiger M, Watson JP. Nontuberculous mycobacteria 
in non-HIV pa6ents: epidemiology, treatment and response. Eur Respir J 2004;23:741–6 
20. Gerogianni I, Papala M, Kos6kas K, Pe6naki E, Gourgoulianis KI. Epidemiology and clinical 
signiﬁcance of mycobacterial respiratory infec6ons in Central Greece. Int J Tuberc Lung Dis 
2008;12:807–12
21. van Ingen J, Bendien SA, de Lange WC, Hoefsloot W, Dekhuijzen PN, Boeree MJ, et al. 
Clinical relevance of non-tuberculous mycobacteria isolated in the Nijmegen-Arnhem 
region, the Netherlands. Thorax 2009;64:502–6  

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
22. Chalmers JD, Aliber6 S, Polverino E, Vendrell M, Crichton M, Loebinger M, Dimakou K, 
Cli%on I, van der Eerden M, Rohde G, Murris-Espin M, Maseﬁeld S, Gerada E, Shteinberg M, 
Ringshausen F, Haworth C, Boersma W, Rademacher J, Hill AT, Aksamit T, O'Donnell A, 
Morgan L, Milenkovic B, Tramma L, Neves J, Menendez R, Paggiaro P, Botnaru V, Skrgat S, 
Wilson R, Goeminne P, De Soyza A, Welte T, Torres A, Elborn JS, Blasi F. The EMBARC 
European Bronchiectasis Registry: protocol for an interna6onal observa6onal study. ERJ 
Open Res. 2016 Jan 20;2(1). 
Figure 1. IRENE centers 

/02/50320625 
Dipartimento delle Units multispecialistiche e dei Trapianti – Area Cardiopolmonare  
U.O.C. Broncopneumologia - Direttore: Prof Francesco Blasi 
Direzione Tel. 02 55033781-2/02 50320627-3 Fax 02/50320625 
Reparto Tel 02/55033789 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it
U.O.S Fibrosi Cistica Sez . Adulti – Responsabile: Dr.ssa Giovanna Pizzamiglio 
Tel. 02 55032503 Fax 02/55034150     Mail: broncopneumologia@policlinico.mi.it