Aggiornamento
La discinesia ciliare primitiva
PRIMARY CILIARY DYSKINESIA
MARIO CANCIANI, MASSIMILIANO DON
Servizio di Allergo-Pneumologia, Clinica Pediatrica, Università di Udine
Luglio 2004 - pagg. 425 -433
Abstract
Primary ciliary dyskinesia (PCD) is a rare condition, which may appear to paediatricians, general
practitioners, ENT specialists as well as in the infertility clinic. The Authors provide a review
of the morphology and function of respiratory cilia and emphasis is placed on the importance
of muco-ciliary clearance as the most important defence mechanism of the upper
and lower airways. A description of changes of the microtubular pattern is given, which can
influence ciliary activity and muco-ciliary transport. Since the diagnosis of PCD leads to modifying
the management of the upper respiratory infections as well as the course of the disease
and particularly the perspectives for lung damage, it is important to consider it among the differential
diagnoses of recurrent and chronic respiratory disease and refer the patient to specialized
centres. Specialized management must be started and continued lifelong.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
1. Buchdal RM, Reiser J, Ingram D, Rutman
A, Cole PJ, Warner JO. Ciliary abnormalities in
respira-tory disease. Arch Dis Child 1988;
63:238-243.
2. Barlocco EG, Valletta EA, Canciani M, Lungarella G, Gardi C, De Santi M, Mastella G. Ultra- structural ciliary defects in children with recurrent infections of the lower respiratory tract. Ped Pulmonol 1991;10:11-17.
3. Afzelius BA. Immotile cilia syndrome: past, present, and prospects for the future. Thorax 1998;53,10: 894-897.
4. Canciani M, Barlocco EG, Mastella G, De Santi MM, Gardi C, Lungarella G. The saccharin method for testing mucociliary function in patients suspected of having primary ciliary dyskinesia. Ped Pul-monol 1988;5:210- 214.
5. Santamaria F, de Santi MM, Grillo G, Sarnelli P, Caterino M, Greco L. Ciliary motility at light microscopy: a screening technique for ciliary defects? Acta Paediatr 1999;88:853-7.
6. Lundberg JON, Weitzberg E, Nordvall SL, et al. Primarily nasal origin of nitric oxide and absence in Kartagener ‘s syndrome. Eur Respir J 1994;7:1501-1504.
7. Karadag B, James AJ, Gultekin E, et al. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J 1999;13:1402-1406.
8. Meeks M, Bush A. Primary ciliary dyskinesia (PCD). Pediatr Pulmonol 2000;29:307-316.
9. Jain B, Rubenstein B, Robbins RA, et al. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun 1993;191:83-88.
10. Baraldi E, Azzolin NM, Biban P, Zacchello F. Effect of antibiotic therapy on nasal nitric oxide concentration in children with acute sinusitis. Am J Crit Care Med 1997;155:1680- 1683.
11. Grasemnn H, Gartig SS, Wiesemann HG, et al. Effect of l-arginine infusion on airway NO in cystic fibrosis and primary ciliary dyskinesia syndrome. Eur Respir J 1999;13:114- 118.
12. Kobzic L, Bredts DS, Lovenstein CJ, et al. Nitric oxide synthase in human and rat lung: immunocyto-chemical and histochemical localization. Am J Resp Cell Mol Biol 1994;9:371- 377.
13. Xue C, Botkin SJ, John RA. Localization of endothelial NOS at the basal microtubule membrane in ciliated epithelium of rat lung. J Histochem Cytochem 1996;44:463-471.
14. Baraldi E, Azzolin N, Carrà S, Zacchello F. Application of exhaled nitric oxide measurement in paediatrics. Eur Respir Rev 1999; 9:68,234-240.
15. Verra F, Fleury-Feith J, Boucherat M, et al. Do nasal ciliary changes reflect bronchial changes? An ultrastructural study. Am Rev Respir Dis 1993;147:908-913.
16. Giorgi PL, Oggiano N, Kantar A, Fabbrizi E, Piatti G, Braga PC. Analysis of respiratory cilia motion and beat frequency counting in screening for Primary Ciliary Dyskinesia in pediatric age. Riv Ital Pediatr (IJP) 1991; 17:707-711.
17. Pifferi M, Cangiotti AM, Ragazzo V, et al. Primary ciliary dyskinesia: diagnosis in children with in-conclusive ultrastructural evaluation. Pediatr Allergy Immunol 2001;12:274- 282.
18. Sun SS. The role of rhinoscintigraphy in the evaluation of nasal mucociliary clearance function in patients with sinusitis. Nucl Med Commun 2000;21(11):1029-1032.
19. Baldi S. Studio del trasporto mucociliare del polmone: i metodi clinici di analisi. Pneumol Pediatr 2002;6:32-39.
20. Canciani M, Lungarella G. Le sindromi da dismotilità ciliare. Medico e Bambino 1990; 8:15-20.
21. Canciani M, Warner JO. Diagnosis and treatment of ciliary dyskinesia on the basis of patient histories. In: Canciani M, Warner JO. Primary Ciliary Dyskinesia from childhood to adulthood. European Respiratory Society, Lausanne (CH), 2000.
22. Cowan MJ, Gladwin MT, Shelhamer JH. Disorders of ciliary motility. Am J Med Sci 2001;321(1):3-10.
23. Whitelaw A, Evans A, Corrin B. Immotile cilia syndrome: a new cause of neonatal respiratory distress. Arch Dis Child 1981; 56: 432- 435.
24. Gemou Engesaeth V, Warner JO, Bush A. New associations of primary ciliary dyskinesia syndrome. Pediatr Pulmonol 1993; 16: 9-12.
25. Baruch GR, Gottfried E, Pery M, Sahin A, Etzioni A. Immotile cilia syndrome including polysplenia, situs inversus and extrahepatic biliary atresia. Am J Med Genet 1989; 33: 390- 3.
26. Greenstone M, Jones RWA, Dewar A, Neville BGR, Cole PJ. Hydrocephalus and primary ciliary dyskinesia. Arch Dis Child 1984; 59: 481-2.
27. Jabourian Z, Lublin DF, Adler A, Gonzales C, Nortrup B, Zwillenberg D. Hydrocephalus in Kartagener’s syndrome. Ear Nose Throat J 1986; 65: 468-72.
28. Greenstone M, Rutman A, Dewar A, Mackay I, Cole PJ. Primary ciliary dyskinesia: cytological and clinical features. Quarterly Journal of Medicine 1988; 67: 405-23.
29. de Boode WP, Collins JM, Veerman AJ, van der Baan S. Primary ciliary dyskinesia: a question- naire study of the clinical aspects. Nederlands Tijdschr Geneeskd 1989; 133: 2338- 41.
30. Pedersen M, Mygind N. Rhinitis, sinusitis and otitis media in Kartagener’s syndrome (primary ciliary dyskinesia). Clinical Otolaryngology 1982; 7: 373-80.
31. Mygind N, Pedersen M. Nose-, sinus-, and ear-symptoms in 27 patients with primary ciliary dyskinesia. Eur J Respir Dis 1983; Suppl 127: 96-101.
32. Afzelius BA. A human syndrome caused by immotile cilia. Science 1976; 193: 317-9.
33. Afzelius BA, Eliasson R. Male and female infertility problems in the immotile cilia syndrome. Eur J Resp Dis 1983;64:144-7.
34. Munro NC, Currie DC, Lindsay KS, et al. Fertility in males with primary ciliary dyskinesia presenting with respiratory infection. Thorax 1994;49: 684-7.
35. Coren ME, Meeks M, Morrison I, Buchdahl RM, Bush A. Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta Pediatrica 2002;91(6):667-9.
36. Bromiker R, Neeman Z, Bar-Oz B, Avital A, Bar-Ziv J, Sprinter C. Early diagnosis of primary ciliary dyskinesia in a newborn without situs inversus. Acta Paediatr 2002;91(9):1002- 5.
37. Chapelin C. Incidence of primary ciliary dyskinesia in children with recurrent respiratory diseases. Ann Otol Rhinol Laryngol 1997; 106(10):854-8.
38. Bush A, Cole P, Hariri M, Mackay I, Phillips G, O’Callaghan C, Wilson R, Warner JO. Primary ciliary dyskinesia: diagnosis and standards of care. Eur Respir J 1998;12:982- 988.
39. White BL, Catlin FI, Stenback WA, Hawkins ED, Seilheimer DK. The immotile cilia syndrome – one cause of persistent upper respiratory infection. Int J Ped Otor 1980;2: 337-346.
40. Greenstone M, Stanley P, Cole P, Mac Kay I. Upper airway manifestations pf primary ciliary dyskinesia. J Lar Otol 1985;99:985-991.
41. Canciani M, Mastella G. Efficacy of Beclomethasone Nasal Drops, Administered in the Moffat’s Position for Nasal Polyposis. Acta Paediatr Scand 1988; 77:612-3.
42. Rossman CM, Newhouse MT. Primary Ciliary Dyskinesia: evaluation and management. Pediatr Pulmonol 1988;5:36-50.
43. Denoyelle F, Roger G, Ducroz V, Escudier E, Faroux B, Garabedian EN. Results of tympanoplasty in children with Primary Ciliary Dyskinesia. Arch Otol Head Neck Surg 1998; 124:177-179.
44. Ellerman A, Bisgaard H. Longitudinal study of lung function in a cohort of primary ciliary dyskinesia. Eur Respir J 1997;10:2376- 2379.
45. Canciani M, Barlocco EG, Cazzola GA, et al. The association of supernumerary microtubules and immotile cilia syndrome and defective neutrophil chemotaxis. Acta Paediatr Scand 1988;77:606-607.
46. Kollberg H, Mossberg B, Afzelius BA, Philipson K, Camner P. Cystic fibrosis compared with the immotile cylia syndrome. Scand J Respir Dis 1978;59:297-306.
47. Grenier P, Cordeau MP, Beigelman C. High- resolution computed tomography of the airways. J Thorac Imaging 1993;31:213-229.
48. Leigh MW. Primary Ciliary Dyskinesia. In Chernick V, Boat TF. Kendig’s disorders of the respiratory tract in children. Philadelphia, Pennsylvania: WB Saunders Co., 6th ed., 1998:819-825.
49. Van der Schans CP, Postma DS, Koeter GH, Rubin BK. Physiotherapy and bronchial mucus transport. Eur Respir J 1999;13:1477- 1486.
50. McCoy K, Hamilton S, Johnson C for the Pulmozyme Study Group. Effects of 12-Week Administration of Dornase Alfa in Patients With Advanced Cystic Fibrosis Lung Disease. Chest 1996;110(4):889-95.
51. Anzuelo A, Jubran A, Ohar JA, Piquette CA, Rennard SI, Colice G, Pattishall EN, Barrett J, Engle M, Perret KA, Rubin BK. Effects of aerosolized surfactant in patients with stable chronic bronchitis. A prospective randomized controlled trial. JAMA 1997;278:1426- 1431.
52. Phillips GE, Thomas S, Heatther S, Bush A. Airway response of children with primary ciliary dyskinesia to exercise and β2-agonist challenge. Eur Respir J 1998;11:1389-1391.
53. Hellinckx J, Demedts M, De Boeck K. Primary Ciliary Dyskinesia: evaluation of pulmonary function. Eur J Pediatr 1998;157:422-426.
54. Corkey CWB, Levison H, Turner JAP. The immotile cilia syndrome. A longitudinal survey. Am Rev Respir Dis 1981;124:544-548.
55. De Santi MM, Magni A, Valletta EA. Gardi C, Lungarella G. Hydrocephalus, bronchiectasis and ciliary aplasia. Arch Dis Child 1990; 65:543-544.
56. Jabourian Z, Lublin FD, Adler A, Gonzales C, Northrup B, Zwillinger D. Hydrocephalus in Kartagener’s syndrome. Ear Nose Throat J 1986;65:468-472.
57. Pradal U. La Discinesia Ciliare Primitiva. Aggiornamenti di Fisiopatologia e Terapia in Pediatria. A cura di Assael BM, 2000;10:80-87.
58. Seegers D, Dankert-Roelse JE, Pals G. Fertility in Primary Ciliary Dyskinesia? Primary Ciliary Dyskinesia – Second European Community Joint Meeting edited by Canciani M and Lungarella G – March 7-8, 1997;37-45. Salzburg, Austria.
59. Jorissen M, Willems T, Van der Schueren D, Van der Schueren B, Decorte R. Male (in)fertility in PCD. Primary Ciliary Dyskinesia – Third European Community Joint Meeting edited by Canciani M and Lungarella G – March 19-21, 1998;23-27. Naples, Italy.
60. Bush A, O’Callaghan C. Primary ciliary dyskinesia. A nose for a diagnosis? Arch Dis Child 2002;87:363-365.
61. Gierich J. Primary ciliary dyskinesia in situs inversus without bronchiectasis. Pneumology 1997;51(12):1127-32.
2. Barlocco EG, Valletta EA, Canciani M, Lungarella G, Gardi C, De Santi M, Mastella G. Ultra- structural ciliary defects in children with recurrent infections of the lower respiratory tract. Ped Pulmonol 1991;10:11-17.
3. Afzelius BA. Immotile cilia syndrome: past, present, and prospects for the future. Thorax 1998;53,10: 894-897.
4. Canciani M, Barlocco EG, Mastella G, De Santi MM, Gardi C, Lungarella G. The saccharin method for testing mucociliary function in patients suspected of having primary ciliary dyskinesia. Ped Pul-monol 1988;5:210- 214.
5. Santamaria F, de Santi MM, Grillo G, Sarnelli P, Caterino M, Greco L. Ciliary motility at light microscopy: a screening technique for ciliary defects? Acta Paediatr 1999;88:853-7.
6. Lundberg JON, Weitzberg E, Nordvall SL, et al. Primarily nasal origin of nitric oxide and absence in Kartagener ‘s syndrome. Eur Respir J 1994;7:1501-1504.
7. Karadag B, James AJ, Gultekin E, et al. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J 1999;13:1402-1406.
8. Meeks M, Bush A. Primary ciliary dyskinesia (PCD). Pediatr Pulmonol 2000;29:307-316.
9. Jain B, Rubenstein B, Robbins RA, et al. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun 1993;191:83-88.
10. Baraldi E, Azzolin NM, Biban P, Zacchello F. Effect of antibiotic therapy on nasal nitric oxide concentration in children with acute sinusitis. Am J Crit Care Med 1997;155:1680- 1683.
11. Grasemnn H, Gartig SS, Wiesemann HG, et al. Effect of l-arginine infusion on airway NO in cystic fibrosis and primary ciliary dyskinesia syndrome. Eur Respir J 1999;13:114- 118.
12. Kobzic L, Bredts DS, Lovenstein CJ, et al. Nitric oxide synthase in human and rat lung: immunocyto-chemical and histochemical localization. Am J Resp Cell Mol Biol 1994;9:371- 377.
13. Xue C, Botkin SJ, John RA. Localization of endothelial NOS at the basal microtubule membrane in ciliated epithelium of rat lung. J Histochem Cytochem 1996;44:463-471.
14. Baraldi E, Azzolin N, Carrà S, Zacchello F. Application of exhaled nitric oxide measurement in paediatrics. Eur Respir Rev 1999; 9:68,234-240.
15. Verra F, Fleury-Feith J, Boucherat M, et al. Do nasal ciliary changes reflect bronchial changes? An ultrastructural study. Am Rev Respir Dis 1993;147:908-913.
16. Giorgi PL, Oggiano N, Kantar A, Fabbrizi E, Piatti G, Braga PC. Analysis of respiratory cilia motion and beat frequency counting in screening for Primary Ciliary Dyskinesia in pediatric age. Riv Ital Pediatr (IJP) 1991; 17:707-711.
17. Pifferi M, Cangiotti AM, Ragazzo V, et al. Primary ciliary dyskinesia: diagnosis in children with in-conclusive ultrastructural evaluation. Pediatr Allergy Immunol 2001;12:274- 282.
18. Sun SS. The role of rhinoscintigraphy in the evaluation of nasal mucociliary clearance function in patients with sinusitis. Nucl Med Commun 2000;21(11):1029-1032.
19. Baldi S. Studio del trasporto mucociliare del polmone: i metodi clinici di analisi. Pneumol Pediatr 2002;6:32-39.
20. Canciani M, Lungarella G. Le sindromi da dismotilità ciliare. Medico e Bambino 1990; 8:15-20.
21. Canciani M, Warner JO. Diagnosis and treatment of ciliary dyskinesia on the basis of patient histories. In: Canciani M, Warner JO. Primary Ciliary Dyskinesia from childhood to adulthood. European Respiratory Society, Lausanne (CH), 2000.
22. Cowan MJ, Gladwin MT, Shelhamer JH. Disorders of ciliary motility. Am J Med Sci 2001;321(1):3-10.
23. Whitelaw A, Evans A, Corrin B. Immotile cilia syndrome: a new cause of neonatal respiratory distress. Arch Dis Child 1981; 56: 432- 435.
24. Gemou Engesaeth V, Warner JO, Bush A. New associations of primary ciliary dyskinesia syndrome. Pediatr Pulmonol 1993; 16: 9-12.
25. Baruch GR, Gottfried E, Pery M, Sahin A, Etzioni A. Immotile cilia syndrome including polysplenia, situs inversus and extrahepatic biliary atresia. Am J Med Genet 1989; 33: 390- 3.
26. Greenstone M, Jones RWA, Dewar A, Neville BGR, Cole PJ. Hydrocephalus and primary ciliary dyskinesia. Arch Dis Child 1984; 59: 481-2.
27. Jabourian Z, Lublin DF, Adler A, Gonzales C, Nortrup B, Zwillenberg D. Hydrocephalus in Kartagener’s syndrome. Ear Nose Throat J 1986; 65: 468-72.
28. Greenstone M, Rutman A, Dewar A, Mackay I, Cole PJ. Primary ciliary dyskinesia: cytological and clinical features. Quarterly Journal of Medicine 1988; 67: 405-23.
29. de Boode WP, Collins JM, Veerman AJ, van der Baan S. Primary ciliary dyskinesia: a question- naire study of the clinical aspects. Nederlands Tijdschr Geneeskd 1989; 133: 2338- 41.
30. Pedersen M, Mygind N. Rhinitis, sinusitis and otitis media in Kartagener’s syndrome (primary ciliary dyskinesia). Clinical Otolaryngology 1982; 7: 373-80.
31. Mygind N, Pedersen M. Nose-, sinus-, and ear-symptoms in 27 patients with primary ciliary dyskinesia. Eur J Respir Dis 1983; Suppl 127: 96-101.
32. Afzelius BA. A human syndrome caused by immotile cilia. Science 1976; 193: 317-9.
33. Afzelius BA, Eliasson R. Male and female infertility problems in the immotile cilia syndrome. Eur J Resp Dis 1983;64:144-7.
34. Munro NC, Currie DC, Lindsay KS, et al. Fertility in males with primary ciliary dyskinesia presenting with respiratory infection. Thorax 1994;49: 684-7.
35. Coren ME, Meeks M, Morrison I, Buchdahl RM, Bush A. Primary ciliary dyskinesia: age at diagnosis and symptom history. Acta Pediatrica 2002;91(6):667-9.
36. Bromiker R, Neeman Z, Bar-Oz B, Avital A, Bar-Ziv J, Sprinter C. Early diagnosis of primary ciliary dyskinesia in a newborn without situs inversus. Acta Paediatr 2002;91(9):1002- 5.
37. Chapelin C. Incidence of primary ciliary dyskinesia in children with recurrent respiratory diseases. Ann Otol Rhinol Laryngol 1997; 106(10):854-8.
38. Bush A, Cole P, Hariri M, Mackay I, Phillips G, O’Callaghan C, Wilson R, Warner JO. Primary ciliary dyskinesia: diagnosis and standards of care. Eur Respir J 1998;12:982- 988.
39. White BL, Catlin FI, Stenback WA, Hawkins ED, Seilheimer DK. The immotile cilia syndrome – one cause of persistent upper respiratory infection. Int J Ped Otor 1980;2: 337-346.
40. Greenstone M, Stanley P, Cole P, Mac Kay I. Upper airway manifestations pf primary ciliary dyskinesia. J Lar Otol 1985;99:985-991.
41. Canciani M, Mastella G. Efficacy of Beclomethasone Nasal Drops, Administered in the Moffat’s Position for Nasal Polyposis. Acta Paediatr Scand 1988; 77:612-3.
42. Rossman CM, Newhouse MT. Primary Ciliary Dyskinesia: evaluation and management. Pediatr Pulmonol 1988;5:36-50.
43. Denoyelle F, Roger G, Ducroz V, Escudier E, Faroux B, Garabedian EN. Results of tympanoplasty in children with Primary Ciliary Dyskinesia. Arch Otol Head Neck Surg 1998; 124:177-179.
44. Ellerman A, Bisgaard H. Longitudinal study of lung function in a cohort of primary ciliary dyskinesia. Eur Respir J 1997;10:2376- 2379.
45. Canciani M, Barlocco EG, Cazzola GA, et al. The association of supernumerary microtubules and immotile cilia syndrome and defective neutrophil chemotaxis. Acta Paediatr Scand 1988;77:606-607.
46. Kollberg H, Mossberg B, Afzelius BA, Philipson K, Camner P. Cystic fibrosis compared with the immotile cylia syndrome. Scand J Respir Dis 1978;59:297-306.
47. Grenier P, Cordeau MP, Beigelman C. High- resolution computed tomography of the airways. J Thorac Imaging 1993;31:213-229.
48. Leigh MW. Primary Ciliary Dyskinesia. In Chernick V, Boat TF. Kendig’s disorders of the respiratory tract in children. Philadelphia, Pennsylvania: WB Saunders Co., 6th ed., 1998:819-825.
49. Van der Schans CP, Postma DS, Koeter GH, Rubin BK. Physiotherapy and bronchial mucus transport. Eur Respir J 1999;13:1477- 1486.
50. McCoy K, Hamilton S, Johnson C for the Pulmozyme Study Group. Effects of 12-Week Administration of Dornase Alfa in Patients With Advanced Cystic Fibrosis Lung Disease. Chest 1996;110(4):889-95.
51. Anzuelo A, Jubran A, Ohar JA, Piquette CA, Rennard SI, Colice G, Pattishall EN, Barrett J, Engle M, Perret KA, Rubin BK. Effects of aerosolized surfactant in patients with stable chronic bronchitis. A prospective randomized controlled trial. JAMA 1997;278:1426- 1431.
52. Phillips GE, Thomas S, Heatther S, Bush A. Airway response of children with primary ciliary dyskinesia to exercise and β2-agonist challenge. Eur Respir J 1998;11:1389-1391.
53. Hellinckx J, Demedts M, De Boeck K. Primary Ciliary Dyskinesia: evaluation of pulmonary function. Eur J Pediatr 1998;157:422-426.
54. Corkey CWB, Levison H, Turner JAP. The immotile cilia syndrome. A longitudinal survey. Am Rev Respir Dis 1981;124:544-548.
55. De Santi MM, Magni A, Valletta EA. Gardi C, Lungarella G. Hydrocephalus, bronchiectasis and ciliary aplasia. Arch Dis Child 1990; 65:543-544.
56. Jabourian Z, Lublin FD, Adler A, Gonzales C, Northrup B, Zwillinger D. Hydrocephalus in Kartagener’s syndrome. Ear Nose Throat J 1986;65:468-472.
57. Pradal U. La Discinesia Ciliare Primitiva. Aggiornamenti di Fisiopatologia e Terapia in Pediatria. A cura di Assael BM, 2000;10:80-87.
58. Seegers D, Dankert-Roelse JE, Pals G. Fertility in Primary Ciliary Dyskinesia? Primary Ciliary Dyskinesia – Second European Community Joint Meeting edited by Canciani M and Lungarella G – March 7-8, 1997;37-45. Salzburg, Austria.
59. Jorissen M, Willems T, Van der Schueren D, Van der Schueren B, Decorte R. Male (in)fertility in PCD. Primary Ciliary Dyskinesia – Third European Community Joint Meeting edited by Canciani M and Lungarella G – March 19-21, 1998;23-27. Naples, Italy.
60. Bush A, O’Callaghan C. Primary ciliary dyskinesia. A nose for a diagnosis? Arch Dis Child 2002;87:363-365.
61. Gierich J. Primary ciliary dyskinesia in situs inversus without bronchiectasis. Pneumology 1997;51(12):1127-32.