Medical Care

General management

Kartagener syndrome represents a wide array of patients along the clinical spectrum; accordingly, management must be tailored towards each individual patient. Continuous clinical follow up is one of the best means of providing this type of individualized care.

Medical management

Prevention of dwindling pulmonary function is the primary end goal of clinical treatment. Because of the lack of major randomized control trials involving patients with Kartagener syndrome, no firm guidelines exist for management and most of those currently used are modified from prior cystic fibrosis studies.

Barbot et al compiled existing evidence to formulate general clinical recommendations. They include patients having at least biannual clinical visits, which would involve routine spirometry, sputum culture, and, if needed, imaging studies. It was found that antibiotic treatment was effective for exacerbations.^[33]

Antibiotics, intravenous or oral and continuous or intermittent, are used to treat upper and lower airway infections. Although prophylactic antibiotics should be used with great caution in this era of emerging antibiotic resistance, children with primary ciliary dyskinesia are especially good candidates for long-term low-dose preventative antibiotics. New studies have supported prophylactic therapy, with gentamicin demonstrating decreased exacerbation frequency.^[14]

Obstructive lung disease, if present, should be treated with inhaled bronchodilators and aggressive pulmonary toilet. Mucolytics may be helpful. Anecdotal reports indicate that inhaled antibiotics, oral and inhaled corticosteroids, and recombinant human DNAse have been used, but no large studies support the use of these agents.^[34]It has been found that regular bronchodilators, recombinant human deoxyribonuclease (rhDNase), and N -acetylcysteine have not been proven to be effective, but still are used occasionally in attempts at symptomatic relief.

It has been postulated that breaking up mucosal secretions with nebulized hypertonic or normal saline could be effective. No studies have demonstrated efficacy.

Pulmonary physiotherapy and exercise also have been shown in some studies to improve respiratory quality.

The most common infectious organisms affecting children with primary ciliary dyskinesia are Haemophilus influenza and Staphylococcus aureus. All patients should have the pneumococcal vaccine and a yearly flu vaccine in addition to standard childhood immunizations. Few long-term trials to measure clinical outcomes and statistical efficacy have been conducted for most medical management strategies.^[33]

Strippoli et al found a substantial heterogeneity in the management of primary ciliary dyskinesia within and between countries and poor concordance with current recommendations, demonstrating a need to standardize management in this patient population,^[35]as well as better research regarding outcomes to therapy.

Smoking risk

Patients with Kartagener syndrome ultimately have an inefficient mucociliary clearance, which results in the inability to prevent toxic and irritant substances from remaining within the respiratory tract. Without this mechanism, patients are much more prone to the complications of such toxins. Patients who smoke cigarettes or have persistent exposure to second-hand smoke are much more likely to develop reactive pneumonias and respiratory distress.

Smoking has been found to have multiple deleterious effects on respiratory cilia. Baseline ciliary beat frequency is increased to clear the irritant, but when the system has an underlying dysmotility, this becomes a less effective response.^{[14, 23]}Children exposed to cigarette smoke may develop additional structural defects to nasal mucosa, causing ciliary function to further decline.^[36]Additionally, microscopic models have demonstrated that cigarette smoke also can reduce the length of respiratory cilia.^[37]

Ultimately, smoking can cause a more rapid deterioration of lung function in patients with Kartagener syndrome, who lack the usual protective mechanisms. Thus, smoking cessation is critical in the Kartagener patient population, as is avoidance of second-hand smoke.

Surgical Care

Tympanostomy tubes are required to reduce conductive hearing loss and recurrent infections. Many patients undergo repeated tympanostomy tube insertions, often complicated by chronic suppurative otitis media. Chronic otorrhea may require special measures for aural hygiene, such as regular otomicroscopy, acetic acid irrigations, or culture-guided topical or systemic antibiotic therapy. Because of anticipated long-term middle-ear disease, inserting tympanostomy tubes is the most sensible method of maintaining the myringotomy because the tube can be expected to stay in the tympanic membrane longer than routine grommets.

When sinus disease is refractory to medical management, functional endoscopic sinus surgery leads to transient improvement in upper and lower respiratory tract symptoms.^[38]The antiquated procedure of making a nasal antral window underneath the inferior turbinate may have a role in the management of primary ciliary dyskinesia because this procedure relies on gravitational rather than ciliary clearance of mucus.

Lobectomy may have a role in cases of severe bronchiectasis, but this is not specific to patients with Kartagener syndrome. Reports describe patients who have undergone lung transplantation for primary ciliary dyskinesia; however, no studies illustrate long-term efficacy and outcomes.^[14]

Consultations

Consultations from an otolaryngologist, geneticist, pulmonologist, social services agent, or obstetrician/gynecologist or urologist/male fertility specialist (infertility) may be indicated.

Activity

Activities can be performed as tolerated; however, patients usually experience mild limitations in physical tolerance.

Medication

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Media Gallery

Axial CT image showing dextrocardia and situs inversus in a patient with Kartagener syndrome. Image courtesy of Wikimedia Commons.
Axial CT image showing situs inversus (liver and inferior vena cava on the left, spleen and aorta on the right) in a patient with Kartagener syndrome. Image courtesy of Wikimedia Commons.
Normal cilia (A) compared with cilia in Kartagener syndrome with missing dynein arms (B). Image courtesy of Wikimedia Commons.

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Table. Mutations in the Genes that Cause Human Primary Ciliary Dyskinesia^[14]

Table. Mutations in the Genes that Cause Human Primary Ciliary Dyskinesia ^[14]

Human Gene	Human Chromosomal Location	Chlamydomonas Ortholog	Ciliary Ultrastructure in Subjects with Biallelic Mutations	Presence of Laterality Defects	Percentage of Individual with Biallelic Mutations	MIM No.
DNAH5	5p15.2	DHC ?	ODA defect	Yes	15-21% of all PCD, 27-38% of PCD with ODA defects	608644
DNAI1	9p21-p13	IC78	ODA defect	Yes	2-9% of all PCD, 4-13% of PCD with ODA defects	244400
DNAI2	17q25	IC69	ODA defect	Yes	2% of all PCD, 4% of PCD with ODA defects	612444
DNAL1	14q24.3	LC1	ODA defect	Yes	na	614017
CCDC114	19q13.32	DC2	ODA defect	Yes	6% of PCD with ODA defects	615038
TXNDC3 (NME8)	7p14-p13	LC5	Partial ODA defect (66% cilia defective)	Yes	na	610852
DNAAF1 (LRRC50)	16q24.1	ODA7	ODA + IDA defect	Yes	17% of PCD with ODA + IDA defects	613193
DNAAF2 (KTU)	14q21.3	PF13	ODA + IDA defect	Yes	12% of PCD with ODA + IDA defects	612517, 612518
DNAAF3 (C19ORF51)	19q13.42	PF22	ODA + IDA defect	Yes	na	606763
CCDC103	17q21.31	PR46b	ODA + IDA defect	Yes	na	614679
HEATR2	7p22.3	Chlre4 gene model 525994 Phytozyme v8.0 gene ID Cre09.g39500.t1	ODA + IDA defect	Yes	na	614864
LRRC6	8q24	MOT47	ODA + IDA defect	Yes	11% of PCD with ODA + IDA defects	614930
CCDC39	3q26.33	FAP59	IDA defect + axonemal disorganization	Yes	36-65% of PCD with IDA defects + Axonemal disorganization	613798
CCDC40	17q25.3	FAP172	IDA defect + axonemal disorganization	Yes	24-54% of PCD with IDA defects + Axonemal disorganization	613808
RSPH4A	6q22.1	RSP4, RSP6	Mostly normal, CA defects in small proportion of cilia	No	na	612649
RSPH9	6p21.1	RSP9	Mostly normal, CA defects in small proportion of cilia	No	na	612648
HYDIN	16q22.2	hydin	Normal, very occasionally CA defects	No	na	610812
DNAH11	7p21	DHC ß	Normal	Yes	6% of all PCD, 22% of PCD with normal ultrastructure	603339
RPGR	Xp21.1	na	Mixed	No	PCD cosegregates with X-linked retinitis pigmentosa	300170
OFD1	Xq22	OFD1	nd	No	PCD cosegregates with X-linked mental retardation	312610
CCDC164 (C2ORF39)	2p23.3	DRC1	Nexin (N-DRC) link missing; axonemal disorganization in small proportion of cilia	No	na	312610
CA = central apparatus; IDA = inner dynein arm; MIM = Mendelian Inheritance in Man; na = not available; N-DRC = nexin–dynein regulatory complex; ODA = outer dynein arm; PCD = primary ciliary dyskinesia.

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Author

Elena B Willis, MD Resident Physician, Department of Otorhinolaryngology, Albert Einstein College of Medicine, Montefiore Medical Center

Elena B Willis, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Medical Student Association/Foundation, Wilderness Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Margo Rose Tanghetti, DO Chief Resident, Department of Otolaryngology, Oklahoma State University College of Osteopathic Medicine

Margo Rose Tanghetti, DO is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Osteopathic Colleges of Ophthalmology and Otolaryngology-Head and Neck Surgery

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director, Pulmonary Medicine General Practice Unit (F2), Senior Staff and Attending Physician, Division of Pulmonary and Critical Care Medicine, Henry Ford Hospital

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Received research grant from: Sanofi Pharmaceutical.

Chief Editor

John J Oppenheimer, MD Clinical Professor, Department of Medicine, Rutgers New Jersey Medical School; Director of Clinical Research, Pulmonary and Allergy Associates, PA

John J Oppenheimer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, New Jersey Allergy, Asthma and Immunology Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Amgen; GSK; Aquestive; Aimmune<br/>Clinical Adjudication/Data Safety Monitoring Board for AZ, GSK, Abbvie, Sanofi; Executive Editor for Annals of Allergy, Asthma & Immunology; Editor for Medscape; Reviewer for UpToDate; Honoraria from American Board of Allergy and Immunology.

Additional Contributors

Ryland P Byrd, Jr, MD Professor of Medicine, Division of Pulmonary Disease and Critical Care Medicine, James H Quillen College of Medicine, East Tennessee State University

Ryland P Byrd, Jr, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

John P Bent, III, MD Professor, Director of Pediatric Otolaryngology, Departments of Otolaryngology-Head and Neck Surgery and Pediatrics, Albert Einstein School of Medicine; Director, Airway Clinic, Cochlear Implant Program, Children's Hospital at Montefiore

John P Bent, III, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Society of Pediatric Otolaryngology, Society for Ear, Nose and Throat Advances in Children, Society of University Otolaryngologists-Head and Neck Surgeons, Triological Society

Disclosure: Nothing to disclose.

Arvind K Badhey, MD Clinical Assistant Professor , Attending Surgeon, Head and Neck Surgical Oncology and Microvascular Reconstructive Surgery, Department of Otolaryngology, UMass Memorial Health, University of Massuchusetts Medical School

Arvind K Badhey, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Matthew Olearczyk, MD and Esther X Vivas, MD, to the development and writing of this article.