ORIGINAL ARTICLE
Year : 2019 | Volume : 14 | Issue : 1 | Page : 75--82
Immun zat on status n chron c obstruct ve pulmonary d sease: A mult center study from
Turkey
Tevf k Ozlu1, Y lmaz Bulbul1, Derya Ayd n2, Dursun Tatar3, Tul n Kuyucu4, Fatma Erboy5, Handan Inonu Koseoglu6, Ceyda Anar3, Aysel Sunnetc oglu7, P nar Y ld z Gulhan8, Unal Sah n9, Aydanur Ek c10, Serap Duru11, Sev nc Sar nc Ulasl12, Ercan Kurt pek13, S bel Gunay14, RIMPACT Study Invest gators15,
1 Department of Chest D seases, School of Med c ne, Karaden z Techn cal Un vers ty, Trabzon, Turkey 2 Chest D sease Cl n c, Pulmonary D seases Hosp tal, Bal kes r, Turkey
3 Department of Pulmonary D seases, Dr. Suat Seren Pulmonary D seases and Thorac c Surgery Educat on and Research Hosp tal, Izm r,
Turkey
4 Department of Pulmonary D seases, Sureyyapasa Pulmonary D seases and Thorac c Surgery Educat on and Research Hosp tal, Istanbul,
Turkey
5 Department of Chest D seases, School of Med c ne, Bulent Ecev t Un vers ty, Zonguldak, Turkey 6 Department of Chest D seases, School of Med c ne, Gaz osmanpasa Un vers ty, Tokat, Turkey 7 Department of Chest D seases, School of Med c ne, Yuzuncu Y l Un vers ty, Van, Turkey 8 Chest D sease Cl n c, Tosya State Hosp tal, Kastamonu, Turkey
9 Department of Chest D seases, School of Med c ne, Recep Tayy p Erdogan Un vers ty, R ze, Turkey 10 Department of Chest D seases, School of Med c ne, Kırıkkale Un vers ty, Kırıkkale, Turkey
11 Department of Pulmonary D seases, D skap Y ld r m Beyaz d Educat on and Research Hosp tal, Ankara, Turkey 12 Department of Chest D seases, School of Med c ne, Hacettepe Un vers ty, Ankara, Turkey
13 Department of Pulmonary D seases, Konya Educat on and Research Hosp tal, Konya, Turkey 14 Chest D sease Cl n c, Afyon State Hosp tal, Afyon, Turkey
15 ,
Correspondence Address:
Prof. Y lmaz Bulbul
Department of Chest D seases, School of Med c ne, Karaden z Techn cal Un vers ty, 61080 Trabzon Turkey
Abstract
OBJECTIVE: The purpose of th s study s to detect the prevalence and the factors assoc ated w th nfluenza and pneumococcal vacc nat on and outcomes of vacc nat on dur ng 2013–2014 season n pat ents w th chron c obstruct ve pulmonary d sease (COPD) n Turkey. METHODS: Th s was a mult center retrospect ve cohort study performed n 53 d fferent centers n Turkey. RESULTS: Dur ng the study per od, 4968 pat ents were ncluded. COPD was staged as GOLD 1-2-3-4 n 9.0%, 42.8%, 35.0%, and 13.2% of the pat ents, respect vely. Influenza vacc nat on rate n the prev ous year was 37.9%; and pneumococcus vacc nat on rate, at least once dur ng n a l fe t me, was 13.3%. Pat ents w th older age, h gher level of educat on, more severe COPD, and comorb d t es, ex-smokers, and pat ents res d ng n urban areas had h gher rates of nfluenza vacc nat on. Mult var ate log st c regress on analys s showed that advanced age, h gher educat on levels, presence of comorb d t es, h gher COPD stages, and exacerbat on rates were assoc ated w th both nfluenza and
pneumococcal vacc nat on. The number of annual phys c an/outpat ent v s ts and hosp tal zat ons due to COPD
exacerbat on was 2.73 ± 2.85 and 0.92 ± 1.58 per year, respect vely. Pat ents w th older age, lower educat on levels, more severe COPD, comorb d d seases, and lower body mass ndex and pat ents who are male and are res d ng n rural areas and vacc nated for nfluenza had s gn f cantly h gher rates of COPD exacerbat on. CONCLUSIONS: The rates of nfluenza and pneumococcal vacc nat on n COPD pat ents were qu te low, and the number of annual phys c an/outpat ent v s ts and hosp tal zat ons due to COPD exacerbat on was h gh n Turkey. Advanced age, h gher educat on levels, comorb d t es, and h gher COPD stages were assoc ated w th both nfluenza and pneumococcal vacc nat on.
Ozlu T, Bulbul Y, Ayd n D, Tatar D, Kuyucu T, Erboy F, Koseoglu HI, Anar C, Sunnetc oglu A, Gulhan PY, Sah n U, Ek c A, Duru S, Ulasl SS, Kurt pek E, Gunay S, RIMPACT Study Invest gators. Immun zat on status n chron c obstruct ve pulmonary d sease: A mult center study from Turkey.Ann Thorac Med 2019;14:75-82
How to c te th s URL:
Ozlu T, Bulbul Y, Ayd n D, Tatar D, Kuyucu T, Erboy F, Koseoglu HI, Anar C, Sunnetc oglu A, Gulhan PY, Sah n U, Ek c A, Duru S, Ulasl SS, Kurt pek E, Gunay S, RIMPACT Study Invest gators. Immun zat on status n chron c obstruct ve pulmonary d sease: A mult center study from Turkey. Ann Thorac Med [ser al onl ne] 2019 [c ted 2020 Jun 24 ];14:75-82
Ava lable from: http://www.thorac cmed c ne.org/text.asp?2019/14/1/75/249798
Full Text
Chron c obstruct ve pulmonary d sease (COPD) s h ghly prevalent llness, and the prevalence var es throughout the world. An overall COPD prevalence of 7.8%–19.7% s reported n adult populat on.[1],[2],[3],[4],[5],[6],[7] Pat ents usually suffer from cough, sputum, dyspnea, and somet mes acute worsen ng of these symptoms, termed as COPD exacerbat on, espec ally n w nter season. Acute COPD exacerbat ons, wh ch can lead to more frequent phys c an/hosp tal adm ss ons, hosp tal zat ons, l fe-threaten ng compl cat ons, and death, are mostly assoc ated w th tracheobronch al nfect ons and a r pollut on.[8] Acute exacerbat ons are more common n severe COPD cases, and those cases are reported to be referred to the hosp tal 1.5–2.5 t mes per year.[9]
Of the nfect ous COPD exacerbat ons, 40%–60% are known to be related to bacter al nfect ons and 30% are related to resp ratory v ral nfect ons (rh nov ruses, nfluenza v ruses, etc.).[10] Influenza vacc nat on has been shown to reduce outpat ent v s ts, hosp tal zat ons, and mortal ty rates due to COPD exacerbat ons.[11],[12] Pneumococcal vacc ne has also been shown to decrease pneumococcal pneumon a n COPD pat ents.[13],[14] In current pract ce, GOLD gu del nes recommend nfluenza vacc nat on n all COPD pat ents to reduce ser ous llness.[15] S m larly, conjugate and
polysacchar de (PCV13 and PPSV23, respect vely) pneumococcal vacc nes are recommended for all COPD pat ents aged ≥65 years. PPSV s also recommended for younger pat ents (<65 years) w th s gn f cant comorb d cond t ons nclud ng chron c heart or lung d seases.[15]
The purpose of th s study s to detect the prevalence and the factors assoc ated w th nfluenza and pneumococcal vacc nat on and outcomes of vacc nat on dur ng 2013–2014 season n COPD pat ents n Turkey.
Methods
Study des gn
Th s mult center retrospect ve cohort study was carr ed out n 53 d fferent centers n Turkey between December 1, 2014, and January 31, 2015, follow ng approval by the eth cs comm ttee.
Study populat on
Dur ng the study per od, all pat ents (>40 years of age) who were adm tted to these centers w th at least 1 year h story of COPD, d agnosed accord ng to the GOLD cr ter a, and agreed to part c pate n the study were ncluded.[15] Demograph c character st cs and pat ents symptoms were collected, and mod f ed Med cal Research Counc l (mMRC) dyspnea scale was f lled for each pat ent by phys c ans us ng a standard quest onna re, wh ch was completed by face-to-face nterv ews. Whether pat ents had nfluenza vacc nat on n the recent year (Have you been vacc nated for nfluenza n the last year?) and pneumococcal vacc nat on at least once n a l fet me (Have you ever rece ved the pneumococcal vacc ne?) were quest oned. COPD exacerbat on was def ned as worsen ng of resp ratory symptoms requ r ng a phys c an or a hosp tal v s t or hosp tal zat on (How many t mes have you been adm tted to a phys c an or a hosp tal due to worsen ng of your
resp ratory symptoms?/How many t mes have you been hosp tal zed due to worsen ng of your resp ratory symptoms?). Phys c an/hosp tal v s ts and/or hosp tal zat ons due to COPD exacerbat on were also recorded.
Stat st cal analys s
used to compare categor cal var ables. The Kolmogorov–Sm rnov test was used to test for normal d str but on of var ables. The parametr c student's t-test was used for compar ng mean or med an values of normally d str buted data, and the nonparametr c Mann–Wh tney U-test was used to compare data that were not normally d str buted. Factors that were potent al contr butors to vacc nat on (age, gender, educat on, smok ng, body mass ndex, res dent al area, comorb d t es, and COPD sever ty) were analyzed us ng log st c regress on. Mult var ate log st c regress on analys s was used as a stepw se descend ng method from pred ct ve factors w th a s gn f cance <0.05 n the un var ate analys s.
Results
A total of 5135 pat ents were collected from the study centers. However, after exclus on of 167 pat ents due to younger age (≤40 years), repeated records, and pat ents w th m ss ng data, 4968 pat ents were analyzed. Of all pat ents, 4196 were male (84.5%) and the mean age was a 66.5 ± 10.0 years (male: 66.6 ± 9.8, female: 66.1 ± 10.7). Other demograph c character st cs are summar zed n [Table 1].{Table 1}
Influenza and pneumococcal vacc nat on rate
Overall rate of nfluenza vacc nat on was 37.9% (1885/4968, 95% conf dence nterval [CI]: 0.366–0.393) dur ng 2013–2014 seasons. Vacc nat on rates were 41.4% (852/2060, 95% CI: 0.392–0.435) and 39.7% (324/816, 95% CI: 0.364–0.431) n COPD D and C and 36.0% (363/1009, 95% CI: 0.330–0.389) and 32.4% (343/1059, 95% CI: 0.296–0.352) n COPD B and A, respect vely (P < 0.001). Pat ents w th older age, h gher educat on, more severe COPD, and comorb d d seases and also pat ents who are ex-smokers and res d ng n urban area had s gn f cantly h gher rates of nfluenza vacc nat on [Table 1].
Overall rate of pneumococcal vacc nat on was 13.3% (659/4966, 95% CI: 0.123–0.142) at least once dur ng n a l fe t me. S m lar to nfluenza, pneumococcal vacc nat on rates were also s gn f cantly h gher n ex-smokers (15.1% vs. 9.1%, P < 0.001), pat ents w th h gher educat on (un vers ty: 29.8%, secondary/h gh school: 20.0%, elementary school: 11.3% vs. uneducated: 8.3%, P < 0.001), pat ents w th comorb d d seases (15.4% vs. 10.4%, P < 0.001), and pat ents res d ng n urban area (15.1% vs. 8.8%, P < 0.001), except COPD sever ty (COPD D: 15.2%, COPD C: 12.3%, COPD B: 13.9%, and COPD A: 14.4%, P = 0.270). Furthermore, female pat ents had s gn f cantly h gher rates of pneumococcal vacc nat on (16.0% vs. 12.8%, P = 0.017).
Mult var ate log st c regress on analys s showed that advanced age (odds rat o [OR]: 1.519, 95% CI: 1.327–1.738, P < 0.001 and OR: 1.309, 95% CI: 1.084–1.580, P = 0.005), h gher educat on levels (OR: 4.217, 95% CI: 2.990–5.947, P < 0.001 and OR: 6.200, 95% CI: 4.033–9.533, P < 0.001), presence of comorb d t es (OR: 1.207, 95% CI: 1.060–1.374, P = 0.004 and OR: 1.357, 95% CI: 1.126–1.635, P < 0.001), and h gher COPD stages and exacerbat on rates (OR: 1.175, 95% CI: 1.028–1.342, P = 0.018 and OR: 1.518, 95% CI: 1.263–1.824, P < 0.001) were found to be assoc ated w th both
nfluenza and pneumococcal vacc nat on, respect vely [Table 2]. Mult var ate log st c regress on analys s also showed female gender as a factor that contr but ng to (OR: 1.675, 95% CI: 1.288–2.178, P < 0.001) pneumococcal vacc nat on. On the contrary, act ve smok ng was assoc ated w th lower nfluenza and pneumococcal vacc nat on rates (OR: 0.638, 95% CI: 0.501–0.813, P < 0.001 and OR: 0.679, 95%CI: 0.474–0.972, P = 0.034).{Table 2}
Among nfluenza-vacc nated pat ents, 86.3% (1627/1885, 95% CI: 0.846–0.877), 6.3% (119/1885, 95% CI: 0.053–0.075), and 7.3% (139/1885, 95% CI: 0.062–0.086) sa d that they had been vacc nated after the recommendat on of the r
phys c ans, pharmac sts, or others, respect vely. In contrast, among the pat ents unvacc nated, 53.1% (1645/3026, 95% CI: 0.525–0.561) stated that the r phys c an d d not recommend vacc nat on, 12.6% (390/3026, 95% CI: 0.117–0.141) sa d that the vacc ne was neffect ve, and 34.3 (991/3026, 95% CI: 0.311–0.344) reported other reasons.
Annual chron c obstruct ve pulmonary d sease exacerbat on and hosp tal zat on rates
Annual number of COPD exacerbat on requ r ng phys c an/outpat ent v s t was 2.73 ± 2.85 t mes per year and requ r ng hosp tal zat on was 0.92 ± 1.58 t mes per year. Pat ents w th older age (>65), lower educat on levels, more severe COPD, comorb d d seases, and lower BMI and pat ents who are male and are res d ng n rural area and vacc nated for nfluenza had s gn f cantly h gher rates of COPD exacerbat on rates [Table 3].{Table 3}
In th s study, we found that the overall prevalence of nfluenza vacc nat on among COPD pat ents dur ng 2013–2014 season was 37.9% and pneumococcal vacc nat on at least once n a l fet me was 13.3%. A recent study wh ch was performed n western c t es of Turkey showed s m lar vacc nat on rates (36.5% for nfluenza and 14.1% for the
pneumococcus).[16] Influenza and pneumococcus vacc nat on rates were found to be unchanged dur ng th s 8-year per od after a study wh ch was performed n Eastern Black Sea Reg on of Turkey dur ng 2006/2007 season, and n that prev ous study, vacc nat on rates were detected as 33.3% and 12.0%, respect vely.[17] Desp te vacc ne recommended groups are well def ned and vacc nes were re mbursed by Soc al Secur ty Inst tut on, vacc nat on rates rema n low n Turkey. There are vary ng vacc nat on rates n COPD pat ents worldw de. In the PLATINO study wh ch was conducted n 2003 n f ve d fferent Lat n Amer can countr es, nfluenza vacc nat on rate reported to be lower n Caracas (Venezuela) and h gher n Sant ago (Ch le) as 5.1% and 52%, respect vely.[18] A study from Italy by Ch att et al. showed that the nfluenza vacc nat on rate to be 30.5% dur ng 2004/2005 season.[19] One another study from Germany showed 46.5% of pat ents rece ved nfluenza vacc ne and 14.6% rece ved pneumococcal vacc ne dur ng 2002/2003 season.[20] On the other hand, h gher nfluenza vacc nat on rates were reported from Norway (59%, dur ng 2006/2007 season) and from France (73%, dur ng 2010/2011 season).[21],[22] More acceptable vacc nat on rates were reported from Spa n n 2003 for nfluenza (84.2%) and for pneumococcus (65%).[23] However, a recent study reported a small decrease n overall prevalence of nfluenza vacc nat on (62.7%) n Spa n.[24]
Pat ents w th older age, h gher level of educat on, more severe COPD, and comorb d t es and pat ents who were ex-smokers and res d ng n urban areas had h gher rates of nfluenza vacc nat on. S m larly, ex-ex-smokers, pat ents w th a h gher level of educat on and comorb d t es, pat ents res d ng n urban area, and also female pat ents had h gher rates of
pneumococcus vacc nat on. S m lar to our results, the vacc nat on rates were found to be h gher among the h gher educat onal levels,[16],[20],[24],[25],[26],[27] elder pat ents and those w th concom tant d sease,[16],[19],[21] and were found to be lower among act ve smokers.[17],[19],[21] Ar ñez-Fernandez et al. also concluded that the most mportant determ nants of pneumococcus vacc nat on are female gender, advanced age, and sever ty of COPD.[28] In add t on to the some demograph cal character st cs, vacc ne recommendat on by phys c an seems to be an mportant determ nant of vacc nat on. We detected that, of the pat ents be ng vacc nated, 86.3% reported that they took nto cons derat on of the r phys c an's adv ce, wh le 53.1% of pat ents be ng unvacc nated reported that the r phys c an gave no adv ce. Some stud es also emphas ze the mportance of phys c ans' recommendat on n vacc nat on rates.[16],[22] However, some other stud es underl ne the role of pat ents not bel ev ng the effect veness of vacc nes.[29]
Our study showed that the annual number of COPD exacerbat ons requ r ng phys c an/outpat ent v s ts or hosp tal zat ons (2.73 ± 2.85 and 0.92 ± 1.58, respect vely) was h gher than those prev ous stud es.[30],[31] For example, n the TORCH and the UPLIFT stud es, the annual rate of exacerbat ons was 0.85 and 0.73 n treatment groups and 1.13 and 0.85 n placebo groups, respect vely.[30],[31] Our results also showed that pat ents w th older age (>65), lower educat on levels, more severe COPD, comorb d d seases and lower BMI, pat ents who are male, and pat ents who are res d ng n rural area and vacc nated for nfluenza had s gn f cantly h gher rates of COPD exacerbat on. Although we d d not nvest gate the role of pr or exacerbat ons, analys s of the ECLIPSE study showed that the s ngle best pred ctor of exacerbat ons, across all GOLD stages, was a past h story of exacerbat ons.[32] Cons stent to our results, ncreas ng age, sever ty of a rflow
l m tat on, pr or asthma d agnos s, eos noph l a, and comorb d cond t ons were also prev ously conf rmed to be pred ctors of frequent exacerbat ons.[33],[34],[35],[36],[37] On the contrary, we showed that h gher levels of educat on and res dence n urban areas were found to be assoc ated w th reduced r sk of exacerbat on. The assoc at on between h gher level of educat on and less exacerbat on rate was not surpr s ng as well as the res dent al area. We bel eve that the lower rates of exacerbat ons n res dents of urban areas are mostly assoc ated w th more v able and comfortable l v ng cond t ons and a h gher qual ty of l fe. Thus, Suzuk et al. and Hurst et al. reported poorer qual ty of l fe to be assoc ated w th frequent exacerbat ons.[33],[34] On the other hand, we th nk that the h gher rates COPD exacerbat ons n pat ents vacc nated for
nfluenza m ght be assoc ated w th the tendency of vacc nat on among more severe COPD pat ents.
Our study has some l m tat ons. Desp te h gh number of study populat on, our data are mostly dependent on self-report ng of vacc nat on and exacerbat on rates. The val d ty of self-reported vacc nat on status has not been assessed n Turk sh populat on; however, some stud es reported that self-reported vacc nat on status s adequate n Austral an and Amer can pat ents.[38],[39] On the other hand, espec ally recall of pneumococcal vacc nat on may be d ff cult s nce t s performed >5 years ntervals (unt l th s study, only polysacchar de type [PPSV23] was ava lable). S m lar to vacc nat on status, number of exacerbat ons and hosp tal zat ons espec ally n frequent exacerbators m ght be d ff cult to remember.
Conclus ons
Our results demonstrated that nfluenza and pneumococcal vacc nat on rates rema ned subopt mal dur ng 2013–2014 season among COPD pat ents and the number of annual outpat ent v s ts and hosp tal zat ons due to COPD exacerbat ons
was h gh n Turkey. Advanced age, h gher educat on levels, presence of comorb d t es, h gher COPD stages, and exacerbat on rates were assoc ated w th both nfluenza and pneumococcal vacc nat on.
F nanc al support and sponsorsh p N l.
Confl cts of nterest
There are no confl cts of nterest. *RIMPACT Study Invest gators
Okutan O1, Y ld z BP2, Cet nkaya PD3, Arslan S4, Cakmak G5, C rak AK6, Sar oglu N7, Kocak ND8, Akturk UA8, Dem r M9, K l c T10, Dall A11, Hezer H12, Alt ntas N13, Acat M14, Dagl CE15, Karg A16, Yakar F17, K rk l G18, Bacc oglu A19, Ged k C20, Intepe YS21, Karaden z G6, Ony lmaz T22, Saylan B23, Basl lar S23, Sar man N24, Ozkurt S25, Ar nc S8, Kanbay A20, Yazar EE2, Y ld r m Z26, Kad oglu EE27, Gul S2, Sengul A28, Berk S4, D k s OS29, Kurt OK16, Arslan Y30, Erol S6, Korkmaz C31, Balaban A32, Toru Erbay U33, Sogukp nar O8, Uzaslan EK34, Babaoglu E12, Bahad r A2, Bar s SA35, Ugurlu AO36, Ilgazl AH35, F dan F37, Kararmaz E38, Guzel A39, Alzafer S40, Cortuk M14, Hocanl I41, Ortakoylu MG2, Erg nel MS42, Yaman N43, Erbaycu AE6, Dem r A6, Duman D8, Tanr verd H44, Yavuz MY6, Sertogullar ndan B45, Ozyurt S46, Bulcun E19, Yuce GD47, Sar ayd n M48, Ayten O1, Bayraktaroglu M2, Tekgul S6, Erel F7, Seny g t A9, Kaya SB10, Ay k S11, Yaz c O14, Akged k A15, Yasar ZA16, Hayat E17, Kalpakl oglu F19, Sever F6, Sarac P22, Ugurlu E25, Kasapoglu US8, Gunluoglu G2, Dem rc NY26, Bora M29, Talay F16, Ozkara B30, Y lmaz MU6, Yavsan DM31, Cet noglu ED34, Balcan MB36, C ftc T35, Havan A37, Gok A39, N zam M2
1Haydarpasa Hosp tal of Gulhane M l tary Med cal Academy Department of Chest D seases, Istanbul, Pulmonary D seases and Thorac c Surgery Educat on and Research Hosp tals of 2Yed kule, Istanbul, 6Dr. Suat Seren, Izm r and 8Sureyyapasa, Istanbul, Educat on and Research Hosp tals of 3Numune, Adana, 5Hasek , Istanbul, 12Ataturk, Ankara, 23Umran ye, Istanbul, 27Reg onal, Erzurum, 28Der nce, Kocael , 29Sevket Y lmaz, Bursa, 32Evl ya Celeb , Kutahya, 47D skap Y ld r m Beyaz d, Ankara. Departments of Chest D seases School of Med c ne 4Cumhur yet Un vers ty, S vas, 7Bal kes r Un vers ty, Bal kes r, 9D cle Un vers ty, D yarbak r, 10Inonu Un vers ty, Malatya, 11Kat p Celeb Un vers ty, Izm r, 13Nam k Kemal Un vers ty, Tek rdag, 14Karabuk Un vers ty, Karabuk, 15Ordu Un vers ty, Ordu, 16Abant Izzet Baysal Un vers ty, Bolu, 17Bezm alem Vakıf Un vers ty, Istanbul, 18F rat Un vers ty, Elaz g, 19K r kkale Un vers ty, K r kkale, 20Meden yet Un vers ty, Istanbul, 21Bozok Un vers ty, Yozgat, 24Maltepe Un vers ty, Istanbul, 25Pamukkale Un vers ty, Den zl , 26Gaz Un vers ty, Ankara, 31Necmett n Erbakan Un vers ty, Konya, 33Dumlup nar Un vers ty, Kutahya, 34Uludag Un vers ty, Bursa,
35Kocael Un vers ty, Kocael , 37Fat h Un vers ty, Istanbul, 39Ondokuz Mayıs Un vers ty, Samsun, 40Ac badem Un vers ty Bak rköy Hosp tal, Istanbul. 42Osmangaz Un vers ty, Esk seh r, 44Bulent Ecev t Un vers ty, Zonguldak, 45Yuzuncü Y l Un vers ty, Van, 46Recep Tayy p Erdogan Un vers ty, R ze, 48Kocatepe Un vers ty, Afyon, State Hosp tals of 22Mard n, Mard n, 38Toros, Adana, 41S rnak, S rnak. 30Et mesgut M l tary Hosp tal, Ankara, 36Baskent Un vers ty Istanbul Hosp tal, Istanbul, 43Pulmonary D seases Hosp tal, Bal kes r, Turkey
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Wednesday, June 24, 2020
