Prevalence and course of disease after lung resection in primary ciliary dyskinesia: a cohort & nested case-control study

Panayiotis Kouis, Myrofora Goutaki, Florian S Halbeisen, Ifigeneia Gioti, Nicos Middleton, Israel Amirav, Israeli PCD Consortium, Angelo Barbato, Italian PCD Consortium, Laura Behan, Mieke Boon, Nagehan Emiralioglu, Eric G Haarman, Bulent Karadag, Cordula Koerner-Rettberg, Romain Lazor, Swiss PCD Group, Michael R Loebinger, Bernard Maitre, French Reference Centre for Rare Lung Diseases, Henryk Mazurek, Lucy Morgan, Kim Gjerum Nielsen, Heymut Omran, Ugur Özçelik, Mareike Price, Andrzej Pogorzelski, Deborah Snijders, PCD Italian Consortium, Guillaume Thouvenin, French Reference Centre for Rare Lung Diseases, Claudius Werner, Zorica Zivkovic, Claudia E Kuehni, Panayiotis K Yiallouros, Panayiotis Kouis, Myrofora Goutaki, Florian S Halbeisen, Ifigeneia Gioti, Nicos Middleton, Israel Amirav, Israeli PCD Consortium, Angelo Barbato, Italian PCD Consortium, Laura Behan, Mieke Boon, Nagehan Emiralioglu, Eric G Haarman, Bulent Karadag, Cordula Koerner-Rettberg, Romain Lazor, Swiss PCD Group, Michael R Loebinger, Bernard Maitre, French Reference Centre for Rare Lung Diseases, Henryk Mazurek, Lucy Morgan, Kim Gjerum Nielsen, Heymut Omran, Ugur Özçelik, Mareike Price, Andrzej Pogorzelski, Deborah Snijders, PCD Italian Consortium, Guillaume Thouvenin, French Reference Centre for Rare Lung Diseases, Claudius Werner, Zorica Zivkovic, Claudia E Kuehni, Panayiotis K Yiallouros

Abstract

Background: Lung resection is a controversial and understudied therapeutic modality in Primary Ciliary Dyskinesia (PCD). We assessed the prevalence of lung resection in PCD across countries and compared disease course in lobectomised and non-lobectomised patients.

Methods: In the international iPCD cohort, we identified lobectomised and non-lobectomised age and sex-matched PCD patients and compared their characteristics, lung function and BMI cross-sectionally and longitudinally.

Results: Among 2896 patients in the iPCD cohort, 163 from 20 centers (15 countries) underwent lung resection (5.6%). Among adult patients, prevalence of lung resection was 8.9%, demonstrating wide variation among countries. Compared to the rest of the iPCD cohort, lobectomised patients were more often females, older at diagnosis, and more often had situs solitus. In about half of the cases (45.6%) lung resection was performed before presentation to specialized PCD centers for diagnostic work-up. Compared to controls (n = 197), lobectomised patients had lower FVC z-scores (- 2.41 vs - 1.35, p = 0.0001) and FEV1 z-scores (- 2.79 vs - 1.99, p = 0.003) at their first post-lung resection assessment. After surgery, lung function continued to decline at a faster rate in lobectomised patients compared to controls (FVC z-score slope: - 0.037/year Vs - 0.009/year, p = 0.047 and FEV1 z-score slope: - 0.052/year Vs - 0.033/year, p = 0.235), although difference did not reach statistical significance for FEV1. Within cases, females and patients with multiple lobe resections had lower lung function.

Conclusions: Prevalence of lung resection in PCD varies widely between countries, is often performed before PCD diagnosis and overall is more frequent in patients with delayed diagnosis. After lung resection, compared to controls most lobectomised patients have poorer and continuing decline of lung function despite lung resection. Further studies benefiting from prospective data collection are needed to confirm these findings.

Keywords: Ciliary motility disorders (MeSH); Kartagener syndrome (MeSH); Lobectomy.

Conflict of interest statement

DS and MB report grants from Italian Health Ministry and Horizon 2020 respectively, outside the submitted work. All other authors wish to declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Participants selection and data availability. Flowchart of participants’ selection and data availability. From the 22 centers (3415 patients) that were included in the iPCD cohort, 20 centers (2896 patients) agreed to participate and provided data to the study. Of these 163 were patients that underwent lung resection. Of the remaining 2733 patients, we randomly selected 265 controls stratified by age (± 5 years), sex and center. Data availability for cross-sectional and longitudinal case-control analysis as well as data availability for the within cases pre-post lung resection analysis is also displayed
Fig. 2
Fig. 2
The frequency of lung resection among patients in the iPCD cohort by participating centers. The prevalence of lung resection among PCD patients in the iPCD cohort across different centers. Prevalence among all PCD patients is denoted with dark color and prevalence among adult PCD patients is denoted with lighter pattern color. Absolute numbers are displayed in Additional file 1: Table S1 (Additional file 1). AU: Australia; BE: Belgium; CH: Switzerland; CY: Cyprus; DE1: Bochum, Germany, DE2: Muenster, Germany; DE3: Hannover, Germany; DK: Denmark; FR: France; IL: Israel; IT: Italy; NL: the Netherlands; NO: Norway; PL: Poland; RS: Serbia; TR1: Istanbul, Turkey; TR2: Ankara, Turkey; UK1: Paediatric Pulmonology Dept, Brompton, UK; UK2: Adult Pulmonology Dept, Brompton, UK; UK3: Southampton, UK
Fig. 3
Fig. 3
Lung function and BMI z-scores across time in PCD lobectomised patients (n = 18), before and after lung resection and propensity score matched controls (n = 18). The left panel displays the trend of lung function and BMI z-scores across time in 18 lobectomised PCD patients with available data before and after lung resection. The dashed red line represents the average trend for all 18 patients. The dashed black line denotes the zero z-score level. The overall mean pre-resection lung function z-scores were significantly higher compared to post-resection lung function z-scores (FEV1: − 1.77 Vs − 2.69 p-value < 0.001, FVC: − 1.16 Vs − 1.99 p-value: 0.003). BMI z-scores did not differ significantly (0.33Vs 0.22 p-value: 0.669). The right panel displays the trend of lung function and BMI z-scores across time in 18 propensity score matched controls

References

    1. Knowles MR, Daniels LA, Davis SD, Zariwala MA, Leigh MW. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease. Am J Respir Crit Care Med. 2013;188(8):913–922. doi: 10.1164/rccm.201301-0059CI.
    1. Magnin ML, Cros P, Beydon N, Mahloul M, Tamalet A, Escudier E, Clément A, Pointe L, Ducou H, Blanchon S. Longitudinal lung function and structural changes in children with primary ciliary dyskinesia. Pediatr Pulmonol. 2012;47(8):816–825. doi: 10.1002/ppul.22577.
    1. Honoré I, Burgel P. Primary ciliary dyskinesia in adults. Rev Mal Respir. 2016;33(2):165–189. doi: 10.1016/j.rmr.2015.10.743.
    1. Coren M, Meeks M, Morrison I, Buchdahl R, Bush A. Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta Paediatr. 2002;91(6):667–669. doi: 10.1111/j.1651-2227.2002.tb03299.x.
    1. Yiallouros PK, Kouis P, Middleton N, Nearchou M, Adamidi T, Georgiou A, Eleftheriou A, Ioannou P, Hadjisavvas A, Kyriacou K. Clinical features of primary ciliary dyskinesia in Cyprus with emphasis on lobectomized patients. Respir Med. 2015;109(3):347–356. doi: 10.1016/j.rmed.2015.01.015.
    1. Ellerman A, Bisgaard H. Longitudinal study of lung function in a cohort of primary ciliary dyskinesia. Eur Respir J. 1997;10(10):2376–2379. doi: 10.1183/09031936.97.10102376.
    1. Marthin JK, Petersen N, Skovgaard LT, Nielsen KG. Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study. Am J Respir Crit Care Med. 2010;181(11):1262–1268. doi: 10.1164/rccm.200811-1731OC.
    1. Strippoli MP, Frischer T, Barbato A, Snijders D, Maurer E, Lucas JS, Eber E, Karadag B, Pohunek P, Zivkovic Z, Escribano A, O'Callaghan C, Bush A, Kuehni CE. ERS task force onPrimary ciliary dyskinesia in children: management of primary ciliary dyskinesia in European children: recommendations and clinical practice. Eur Respir J. 2012;39(6):1482–1491. doi: 10.1183/09031936.00073911.
    1. Camargos P, Le Bourgeois M, Revillon Y, Tatsuo E, Sermet-Gaudelus I, Scheinmann P, de Blic J. Lung resection in cystic fibrosis: a survival analysis. Pediatr Pulmonol. 2008;43(1):72–76. doi: 10.1002/ppul.20742.
    1. Lucas J, Connett GJ, Lea R, Rolles CJ, Warner JO. Lung resection in cystic fibrosis patients with localised pulmonary disease. Arch Dis Child. 1996;74(5):449–451. doi: 10.1136/adc.74.5.449.
    1. Lucas JS, Connett GJ, Fairhurst J. Long term results of lung resection in cystic fibrosis patients with localised lung disease. Arch Dis Child. 2002;86(1):66. doi: 10.1136/adc.86.1.66.
    1. Sheikh SI, McCoy K, Ryan-Wenger NA, Patel A, Kirkby S. lobectomy in patients with cystic fibrosis. Can Respir J. 2014;21(4):e63–e66. doi: 10.1155/2014/709671.
    1. Emiralioglu N, Dogru D, Yalcin S, Tugcu GD, Yalcin E, Ozcelik U, Ekinci S, Kiper N. Impact of surgery on growth, pulmonary functions, and acute pulmonary exacerbations in children with non-cystic fibrosis bronchiectasis. Thorac Cardiovasc Surg. 2019;67(01):058–066. doi: 10.1055/s-0037-1608922.
    1. Lucas JS, Burgess A, Mitchison HM, Moya E, Williamson M, Hogg C, National PCD, Service U Diagnosis and management of primary ciliary dyskinesia. Arch Dis Child. 2014;99(9):850–856. doi: 10.1136/archdischild-2013-304831.
    1. Smit HJ, Schreurs AJ, Van den Bosch JMM, Westermann CJ. is resection of bronchiectasis beneficial in patients with primary ciliary dyskinesia? Chest. 1996;109(6):1541–1544. doi: 10.1378/chest.109.6.1541.
    1. Goutaki Myrofora, Maurer Elisabeth, Halbeisen Florian S., Amirav Israel, Barbato Angelo, Behan Laura, Boon Mieke, Casaulta Carmen, Clement Annick, Crowley Suzanne, Haarman Eric, Hogg Claire, Karadag Bulent, Koerner-Rettberg Cordula, Leigh Margaret W., Loebinger Michael R., Mazurek Henryk, Morgan Lucy, Nielsen Kim G., Omran Heymut, Schwerk Nicolaus, Scigliano Sergio, Werner Claudius, Yiallouros Panayiotis, Zivkovic Zorica, Lucas Jane S., Kuehni Claudia E. The international primary ciliary dyskinesia cohort (iPCD Cohort): methods and first results. European Respiratory Journal. 2016;49(1):1601181. doi: 10.1183/13993003.01181-2016.
    1. Gail MH. Frequency matching. Statistics Reference Online: Wiley StatsRef; 2005.
    1. Werner C, Onnebrink JG, Omran H. Diagnosis and management of primary ciliary dyskinesia. Cilia. 2015;4(1):2. doi: 10.1186/s13630-014-0011-8.
    1. Lucas JS, Barbato A, Collins SA, Goutaki M, Behan L, Caudri D, Dell S, Eber E, Escudier E, Hirst AR, Hogg C, Jorissen M, Latzin P, Legendre M, Leigh MW, Midulla F, Nielsen KG, Omran H, Papon JF, Pohunek P, Redfern B, Rigau D, Rindlisbacher B, Santamaria F, Shoemark A, Snijders D, Tonia T, Titieni A, Walker WT, Werner C, Bush A, Kuehni CE. European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia. Eur Respir J. 2017;49(1):1601090. doi: 10.1183/13993003.01090-2016.
    1. Becker SO, Ichino A. Estimation of average treatment effects based on propensity scores. Stata J. 2002;2(4):358–377. doi: 10.1177/1536867X0200200403.
    1. Jain K, Padley S, Goldstraw E, Kidd S, Hogg C, Biggart E, Bush A. Primary ciliary dyskinesia in the paediatric population: range and severity of radiological findings in a cohort of patients receiving tertiary care. Clin Radiol. 2007;62(10):986–993. doi: 10.1016/j.crad.2007.04.015.
    1. Cohen-Cymberknoh M, Simanovsky N, Hiller N, Hillel AG, Shoseyov D, Kerem E. Differences in disease expression between primary ciliary dyskinesia and cystic fibrosis with and without pancreatic insufficiency. Chest J. 2014;145(4):738–744. doi: 10.1378/chest.13-1162.
    1. Maglione M, Montella S, Mollica C, Carnovale V, Iacotucci P, De Gregorio F, Tosco A, Cervasio M, Raia V, Santamaria F. Lung structure and function similarities between primary ciliary dyskinesia and mild cystic fibrosis: a pilot study. Ital J Pediatr. 2017;43(1):34. doi: 10.1186/s13052-017-0351-2.
    1. Dettmer S, Ringshausen F, Vogel-Claussen J, Fuge J, Faschkami A, Shin H, Schwerk N, Welte T, Wacker F, Rademacher J. Computed tomography in adult patients with primary ciliary dyskinesia: typical imaging findings. PLoS One. 2018;13(2):e0191457. doi: 10.1371/journal.pone.0191457.
    1. Tadd Katelyn, Morgan Lucy, Rosenow Tim, Schultz André, Susanto Clarissa, Murray Conor, Robinson Philip. CF derived scoring systems do not fully describe the range of structural changes seen on CT scans in PCD. Pediatric Pulmonology. 2019;54(4):471–477. doi: 10.1002/ppul.24249.
    1. Priftis KN, Mermiri D, Papadopoulou A, Anthracopoulos MB, Vaos G, Nicolaidou P. The role of timely intervention in middle lobe syndrome in children. Chest. 2005;128(4):2504–2510. doi: 10.1378/chest.128.4.2504.
    1. Einarsson JT, Einarsson JG, Isaksson H, Gudbjartsson T, Gudmundsson G. Middle lobe syndrome: a nationwide study on clinicopathological features and surgical treatment. Clin Respir J. 2009;3(2):77–81. doi: 10.1111/j.1752-699X.2008.00109.x.
    1. Frija-Masson J, Bassinet L, Honore I, Dufeu N, Housset B, Coste A, Papon JF, Escudier E, Burgel PR, Maitre B. Clinical characteristics, functional respiratory decline and follow-up in adult patients with primary ciliary dyskinesia. Thorax. 2017;72(2):154–160. doi: 10.1136/thoraxjnl-2015-207891.
    1. Shah A, Shoemark A, MacNeill SJ, Bhaludin B, Rogers A, Bilton D, Hansell DM, Wilson R, Loebinger MR. A longitudinal study characterising a large adult primary ciliary dyskinesia population. Eur Respir J. 2016;48(2):441–450. doi: 10.1183/13993003.00209-2016.
    1. Goutaki Myrofora, Halbeisen Florian S., Spycher Ben D., Maurer Elisabeth, Belle Fabiën, Amirav Israel, Behan Laura, Boon Mieke, Carr Siobhan, Casaulta Carmen, Clement Annick, Crowley Suzanne, Dell Sharon, Ferkol Thomas, Haarman Eric G., Karadag Bulent, Knowles Michael, Koerner-Rettberg Cordula, Leigh Margaret W., Loebinger Michael R., Mazurek Henryk, Morgan Lucy, Nielsen Kim G., Phillipsen Maria, Sagel Scott D., Santamaria Francesca, Schwerk Nicolaus, Yiallouros Panayiotis, Lucas Jane S., Kuehni Claudia E. Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort. European Respiratory Journal. 2017;50(6):1701659. doi: 10.1183/13993003.01659-2017.
    1. Aurora P, Wade A, Whitmore P, Whitehead B. A model for predicting life expectancy of children with cystic fibrosis. Eur Respir J. 2000;16(6):1056–1060. doi: 10.1034/j.1399-3003.2000.16f06.x.
    1. McColley SA, Schechter MS, Morgan WJ, Pasta DJ, Craib ML, Konstan MW. Risk factors for mortality before age 18 years in cystic fibrosis. Pediatr Pulmonol. 2017;52(7):909–915. doi: 10.1002/ppul.23715.
    1. Miller MR, Hankinson JATS, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF. Pellegrino R, Viegi G, Werner J. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–338. doi: 10.1183/09031936.05.00034805.

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