1. Introduction

Primary ciliary dyskinesia (PCD) is a hereditary condition, estimated to affect >1 in 7554 individuals.¹ In PCD structural and/or functional cilial impairment leads to impaired mucociliary clearance.¹ The impact of PCD on the respiratory tract is evident through recurrent lower respiratory tract infections, bronchiectasis and chronic sinusitis. Average lung function in children with PCD in the UK is abnormally low.²

Since 2013, all children with PCD in England have been offered disease-specific support from one of the four specialist PCD management centres, arranged with network care at local centres. The physiotherapy English national standards of care for children with PCD³ were developed through collaboration of English paediatric PCD physiotherapists in alignment with the NHS England standard contract.⁴ This document provides an update of the 2018 standards with current research and information. At the time of writing the authors represented England’s four paediatric PCD management centres. Collectively, they have over four decades of experience working with children with PCD as PCD-specialist physiotherapists (PCD-spPTs), with an individual range of 3-12 years. Patient/parent representatives provided guidance during the initial conception and final draft review stages of the standard development. These standards relate to children and young people with a confirmed diagnosis of PCD and those who are under the PCD service, with clinical findings highly suggestive of PCD. Whilst commissioned services may vary between the devolved nations, the principles of good practice would be applicable across UK and potentially beyond.

The Scottish Intercollegiate Guidelines Network⁵ system was used to evaluate all evidence identified through systematic literature searches of major databases (Medline, CINAHL, EBSCO, Cochrane). Quality of recommendations is graded A (highest) to D (lowest) depending on the quality of the evidence available.⁵ With a paucity of PCD specific research evidence from other diseases and anecdotal evidence have been used where appropriate to form the good practice points (GPP). PCD specific research is very much needed, the authors welcome interest for collaboration, working to build this much needed evidence base.

2. Service standards

All people with PCD (PwPCD), living in England and cared for by a paediatric service will have access to a PCD-spPT through specialist PCD management services. If PwPCD are receiving local care, the PCD-spPT will work alongside local respiratory physiotherapists to provide ongoing monitoring and care. As PwPCD may have diverse backgrounds, it is important to strive to for equitable access to physiotherapy services; PwPCD should be able to access regular physiotherapy reviews regardless of their location or background.

Inpatient care

During an inpatient admission, the local physiotherapy team will be responsible for the individual’s respiratory physiotherapy care. PwPCD should be offered supervised, twice-daily airway clearance technique (ACT) sessions whilst on intravenous antibiotics , at least once-daily at weekends. Where resources allow, and as clinically appropriate, physical activity should be considered daily.

Home IVs

The multidisciplinary team (MDT) may consider home intravenous antibiotics for individuals who have demonstrated the ability to consistently complete their home physiotherapy regimen effectively and independently. Individuals should be reviewed by a respiratory physiotherapist at least once during the intravenous antibiotic course.

Outpatient clinic reviews

PwPCD should be seen at least once a year by a PCD-spPT for their annual review. This will be a comprehensive assessment (sections 2-8), depending on the individual’s presentation or clinical needs.

Follow-up out-patient reviews with either the PCD-spPT or a local respiratory physiotherapist (depending on proximity to the specialist centre) should be offered three-monthly, or as clinically indicated.

Virtual reviews

Although virtual reviews offer additional treatment opportunities, they provide limited physical assessment and are not a comparable replacement for face-to-face sessions. Drug-response assessments and establishing a new ACT should be completed in person.

Home visits

PwPCD should be offered a home visit, regardless of location, as clinically indicated e.g. following diagnosis, during treatment adherence challenges. These may be completed by either the local physiotherapist or PCD-spPT.

School visits

Schools should be offered age-appropriate PCD information, including the PCD team’s contact details.

If physiotherapy sessions are required in school, a PCD-spPT will offer appropriate training and updates as required for relevant school staff. Where possible, these should be in person, regardless of location.

New diagnosis

All newly diagnosed PwPCD will be seen by the PCD-spPT within two months of receiving their referral, with priority given to those yet to receive local respiratory physiotherapy input.

Transition to adult services

In the years preceding the transfer to the adult services, physiotherapists should support and encourage independence. This includes: understanding how to complete their daily physiotherapy treatment effectively, action to take when unwell, appropriate equipment maintenance.

The paediatric PCD-spPT will consult with the adult PCD specialist team as needed during transition, and at the time of transfer, provide a handover to both the adult PCD-spPT and local physiotherapists.

Advice and education

Information on the home physiotherapy plan will be provided; this may be verbal, written or include signposting to appropriate online materials. This plan should be shared with their local centres. Wherever possible, accessibility should be considered in the development or review of patient-facing materials. During normal working hours, a telephone/email advisory service is available.

Equipment

Specialist PCD centres can offer; Positive Expiratory Pressure (PEP) devices, oscillatory PEP (OPEP) devices, sinus rinse bottles, standard compressor nebulisers, and mesh nebulisers as indicated.

The PCD specialist centres are not commissioned for mechanical insufflation-exsufflation , non-invasive ventilation , or high frequency chest wall oscillation equipment. However, in exceptional circumstances where clinically indicated, the PCD specialist centres can support the local team with an application for an individual funding request for specialist equipment.

Maintenance of devices including nebulisers and airway clearance adjuncts, which should be in line with manufacturer’s guidelines, is the responsibility of the centre issuing the device.

Clinician training

As autonomous practitioners, all physiotherapists are required to work within their scope of practice and should undertake appropriate training. During normal working hours, the PCD-spPT will be available to provide specialist advice. The PCD-spPT will endeavour to offer joint sessions with local teams for any complex patients.

Clinical standards

The PCD-spPT is responsible for providing local hospitals and physiotherapists with relevant guidelines. The PCD-spPT should be committed to undertaking regular audit and relevant service improvement.

3. Airway clearance techniques

General principles

Recommendations

• PwPCD should be advised on an effective ACT by an appropriately experienced physiotherapist from diagnosis. (D)

• ACT reviews should include both discussion and observation of the regimen. (D)

• An appropriate range of outcome measures should be used to assess the efficacy of ACT regimens. (B)

• Clear guidance on frequency and duration of airway clearance regimens, including advice on any adaptations during exacerbations, should be provided. (D)

• The importance of adequate hydration for effective airway clearance should be discussed as needed. (GPP)

ACTs are recommended at least from the point of diagnosis.² The PCD population is heterogeneous, varied in age, development, and clinical presentation.⁶ While there is currently no evidence on the optimal frequency of ACTs, an effective once or twice daily regimen is commonly recommended. Since the way in which ACTs are performed and guidance may change over time and individual techniques can be suboptimal,⁷ regular reviews are advised.

A range of outcome measures are available to assess lung health and treatment effects, but all current measures have limitations. Whilst spirometry is widely available, forced expiratory volume in the first second (FEV₁), is less sensitive to detect abnormalities in PCD than computerised tomography scans or the lung clearance index.^8–11 No significant change has been seen in FEV₁ or lung clearance index following a single ACT session.¹² Sputum volume and weight can be unreliable^13,14 and between-clinician auscultation concordance is moderate to poor.^15,16 In the absence of a gold standard method for assessing the effects of ACTs, employing multiple outcomes may be advisable.¹⁴

Coughing can be a stigma for PwPCD,¹⁷ so if a daily cough is not reported, it is important to ensure that this is not due to under-reporting of symptoms or cough suppression. During periods of increased secretions or difficulties in clearance, regimen modifications may be required to ensure it is effectively meeting the current needs.

Whilst there is limited evidence in anaesthetic management of PCD, consideration should be given to effective pre-operative secretion clearance¹⁸ and post-operative review.

Regimen content

Recommendations

• ACT regimens should be tailored for individuals. (C)
• Individual advice should be given on positioning during airway clearance. (D)
• When selecting an airway clearance intervention, the following should be considered:
  • Breathing techniques including the Active Cycle of Breathing Technique and Autogenic Drainage. (D)
  • PEP or OPEP device. The way in which an individual uses a device can be personalised and should be reviewed regularly. (D)
  • Manual techniques (percussion, vibrations) should be taught by a qualified physiotherapist and performance reviewed periodically. (D)
• Physiotherapists should be aware of relevant contraindications and precautions. (GPP)
• A minority of individuals may be unable to achieve regular effective airway clearance with standard interventions, for example due to comorbidities or disease severity. In such cases, it may be appropriate to consider alternatives or additional components. (GPP) (see section 1).
• Appropriate instructions on ACT device cleaning and maintenance should be given. (D)

There are a range of ACTs available and ways in which they can be employed. There is currently no evidence to support superiority of one technique either short or long-term, therefore individually tailored ACT regimens are widely recommended¹⁹ and used.² The tailoring of ACT regimens can involve consideration of the individual’s presentation, age, ability, preferences, the regimen properties, treatment aims and regimen response.¹⁹ In PCD, dysfunction is seen in the peripheral airways¹¹ and bronchiectatic changes are most common in the middle and lower lobes.^20–23 Consideration should be given to the physiological principles of ACTs^19,24:

• Inclusion of strategies with an expiratory airflow bias to mobilise secretions proximally,²⁴ for example, breathing techniques that can be introduced as age appropriate with time and guidance to optimise their effects.

• Positioning can influence regional ventilation²⁵ and lung volumes during airway clearance.²⁶

• Physiologically, PEP devices can facilitate the splinting and ventilation of obstructed smaller airways²⁷ and OPEP devices may oscillate at frequencies similar to healthy ciliary beat frequency²⁸

There is no evidence to indicate superiority of one PEP or OPEP device, a summary of PCD studies pertaining to this is provided in the online supplement. No evidence is currently available on the efficacy of Simeox® in PCD.

ACT contraindications and precautions should be considered on an individual basis. ACT devices can be contaminated after routine use and, while the clinical implication of this unclear,^29,30 cleaning should follow local infection prevention and manufacturers’ recommendations.

Exercise for airway clearance is discussed in section 6.

4. Inhaled medicines used to facilitate airway clearance

Nebulised Isotonic and hypertonic saline

Recommendations

• Hypertonic saline (3%, 6% or 7%) should be considered to enhance the effectiveness of ACTs, considering an individual’s clinical symptoms. (D)
• Isotonic saline (0.9%) may be appropriate in those who do not tolerate hypertonic saline. (D)
• A drug response assessment should be conducted for the initial ‘test dose’ of hypertonic saline to confirm safety and suitability (see online supplement). This should be conducted face-to-face. (D)
• If bronchoconstriction symptoms are present following use of nebulised hypertonic, the drug response assessment should be repeated. Clinical reviews should include periodic assessment of emerging adverse effects. (GPP)
• If evidence of bronchoconstriction is seen during the drug-response assessment, consider introducing a bronchodilator. The assessment should be repeated with bronchodilator pre-hypertonic saline. (D)
• Advice should be given on the most appropriate timing and application of Nebulised isotonic and hypertonic saline within the ACT current routine. (D)
• Whilst all elements of the suggested treatment routine below are not prescribed universally, the order of treatment should be:
  • inhaled bronchodilator,
  • Isotonic or hypertonic saline,
  • airway clearance,
  • inhaled antibiotic therapy,
  • inhaled preventer (steroid). (GPP)
• Consider combining saline with an ACT device to reduce treatment burden. (D)

Nebulised hypertonic saline which draws water into the airways through osmosis, can improve mucus hydration and ease expectoration.³¹ It is both recommended³² and commonly used in PCD. It has been shown to be effective, well tolerated and a safe adjunct to ACTs.³³ Short-term benefits from hypertonic saline demonstrated in adults with non-CF bronchiectasis include improved quality of life, lung function, increased ease and amount of sputum expectorated.³⁴

Recombinant DNase

Recommendations

• Recombinant human deoxyribonuclease (rhDNase) is not routinely recommended or funded. A trial should be considered on a case-by-case basis. (D)
• A drug-response assessment should be conducted for the initial dose of rhDNase to confirm safety and suitability (see Appendix A). (D)
• Advice should be given about the timing of rhDnase in relation to the ACT regimen (GPP)

Inhaled rhDNase breaks down DNA within sputum, reducing its viscoelasticity, to aid expectoration. While rhDNase is highly effective in the management of individuals with CF, there is conflicting evidence in PCD (see online supplement). RhDNase is currently not recommended for routine use in PwPCD.³⁵

Inhaled medication

Recommendations

• A spacer device should be used with metered dose inhalers. (GPP)
• Inhaler technique should be assessed periodically and optimised by the MDT. (GPP)

For more information, please see further guidance on inhaler use from Asthma and Lung UK.³⁶

5. Sinonasal management

Recommendations

• Every review should include an assessment of upper airway symptoms. (GPP)
• Sinonasal management should be commenced and re-assessed as appropriate on an individual basis. (GPP)
• Assessment and management for conditions that may exacerbate sinonasal symptoms (for example: allergy or hay fever), should be performed by an appropriate member of the MDT. (GPP)
• Consideration should be given to the role of the nose in the context of breathing patterns. (GPP)Advice on timing of airway clearance and nasal management should be given. (GPP)

As nasal symptoms of a persistent nature are characteristic of PCD,³⁷ the management of sinonasal symptoms is considered part of routine PCD care. Hypoplastic sinuses are seen in PwPCD,³⁸ yet there is currently no consensus on the management of chronic rhinosinusitis in PCD.³⁹ As the sinuses may function as a bacterial reservoir,^40–42 consideration should be given to effective management of the upper airways and sinuses. As paranasal sinuses development continues until early adulthood,⁴³ regular assessment and treatment reviews are required. In the early years, nebulised medication delivered via a face mask may be beneficial in targeting upper airway clearance.

Sinonasal irrigation is recommended for the management of chronic rhinosinusitis in children, with isotonic irrigation solutions being better tolerated than hypertonic solutions.^44,45 Whilst nasal irrigation may aid effective sinonasal clearance, its use should be individualised based on age, developmental ability, assessment findings and precautions. It is safe, cheap and usually a well-tolerated option for symptom relief and to prevent bacterial growth.^46,47 Guidance should be given on the correct solution preparation and irrigation technique. If sinonasal management is well established and effective, consideration may be given to switching to a nebuliser mouthpiece to bias administration to the lower airways.

Sinonasal nebulisation may be considered as targeted clearance therapy or infection eradication, although there is no evidence to support this.

6. Exercise

Recommendations:

• Daily cardiovascular exercise should be strongly encouraged. (C)
• Exercise should not be considered a substitute for ACTs. (D)
• Physical activity advice should be individually tailored. (D)Exercise testing should be considered in PwPCD. (D)

As the reduced exercise capacity seen in PwPCD^48,49 has been linked to reduced pulmonary function,⁵⁰ PwPCD should strive to achieve equitable activity levels to those without disease. Assessment of physical activity habits, and exercise advice should be included in physiotherapy consultations. The current UK physical activity guidelines for healthy children^51,52 are applicable to children with PCD (See online supplement).

Exercise, combined with FETs and coughs, is used to enhance the clearance of bronchial secretions in people with cystic fibrosis,⁵³ but there is currently no evidence of its efficacy as an ACT.⁵⁴ However, it is appropriate to encourage PwPCD to expectorate during and post-exercise.

Although cardiopulmonary exercise testing offers reproducible data,⁵⁵ to identify a reduction in exercise capacity and inform exercise programmes, access to this can be limited. There is no evidence to suggest a specific field test is superior in the paediatric PCD population.

7. Urinary incontinence

Recommendations:

• Urinary incontinence screening or assessment should be considered in individuals aged eight years and above. (D)
• Education on pelvic floor exercises should be initiated as needed, with timely specialist input referrals when indicated. (GPP)

Urinary incontinence occurs within the paediatric PCD population,^56,57 but reported prevalence varies. A higher incidence of urinary incontinence is seen in other conditions with chronic coughing which increases pressure on the pelvic floor.^58,59 Urinary incontinence can impact performance of airway clearance, exercise and spirometry.⁶⁰ As such, screening for urinary incontinence should be completed for children with PCD, with advice given and referral to specialist services where indicated.

8. Posture, assessment and management of musculoskeletal issues

Recommendations:

• Screening for the musculoskeletal) symptoms is advised from the age of eight years. (GPP)
• Where musculoskeletal concerns are identified, further assessment or follow-up by a musculoskeletal physiotherapist may be indicated. (GPP)
• PwPCD should be advised on posture, flexibility, muscle strength and activity levels. (GPP)

Musculoskeletal issues that are common in chronic suppurative lung diseases have a significant impact on an individual’s quality of life.^59,61 Musculoskeletal dysfunction (reduced range of thoracic spine movement, pain, stress incontinence) is seen in 50% of children and young people with PCD⁶² and postural abnormalities are more common in PwPCD than their healthy peers.⁴⁹ As comorbidities, such as cardiac surgery, can alter thoracic biomechanics, some may require screening for musculoskeletal issues at a younger age.

Musculoskeletal assessment and advice on physical activity to promote strength, flexibility and bone health should be part of routine PCD care. The management of musculoskeletal symptoms may require referral on to specialist teams. Physical activity presents an opportunity to optimise posture and prevent or improve musculoskeletal symptoms (see section 6).

9. Adherence to management

Recommendations

• Time should be given during consultations to understand the individual’s adherence patterns and behaviours. (B)
• When discussing adherence patterns and behaviours, consideration should be given to habit formation, self-management and educational strategies. (GPP)
• Treatments should be rationalised or combined, where possible and appropriate, to offer the simplest and most effective treatment regimen possible. (C)

As the treatment burden in PCD can be high,⁶³ adherence to treatments is an important part of consultations. Poor adherence can affect FEV₁ in PCD,⁶⁴ lead to increased morbidity,⁶⁵ and a financial burden on health services. Continuing adherence can be affected by psychological problems, non-trustful relationships with healthcare providers, perceived treatment efficacy, time-consuming regimes, health literacy and cultural differences.^65,66 These should be discussed, identified, and addressed appropriately, with clinicians working alongside PwPCD, to monitor engagement, identify barriers and support adherence.⁶⁶ Behaviour change interventions can have a positive influence on adherence⁶⁷ and may be useful in practice.

Conflicts of interest

The authors do not have any financial and personal relationships with other people or organisations that could inappropriately influence the work.

Acknowledgements

The PCD management team consultants for their review and support of the standards. Patient and parent representatives for their guidance on the initial outline of the standards update (LD) and review of the final document (SS).

• 1.

  Hannah WB, Seifert BA, Truty R, Zariwala MA, Ameel K, Zhao Y, et al. The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: a genetic database analysis. The Lancet Respiratory Medicine. 2022;10(5):459-468. doi:10.1016/​S2213-2600(21)00453-7. PMID:35051411
• 2.

  Rubbo B, Best S, Hirst RA, Shoemark A, Goggin P, Carr SB, et al. Clinical features and management of children with primary ciliary dyskinesia in England. Archives of Disease in Childhood. 2020;105(8):724-729. doi:10.1136/​archdischild-2019-317687
• 3.

  Schofield LM, Lloyd N, Kang R, Marsh G, Keenan V, Wilkins HM. Physiotherapy English national standards of care for children with primary ciliary dyskinesia. Journal of ACPRC. 2018;50:72-82.
• 4.

  NHS England. 2013/2014 NHS standard contract for primary ciliary dyskinesia (PCD) managment service (children). In: England N, ed. NHS England; 2013. https:/​/​www.england.nhs.uk/​wp-content/​uploads/​2018/​08/​primary-ciliary-dyskinesia-management-service-children-v2.pdf
• 5.

  Scottish Intercollegiate Guidelines Network SIGN 50. A Guideline Developers’ Handbook.; 2011.
• 6.

  Kinghorn B, Rosenfeld M, Sullivan E, Onchiri F, Ferkol TW, Sagel SD, et al. Airway Disease in Children with Primary Ciliary Dyskinesia: Impact of Ciliary Ultrastructure Defect and Genotype. Annals of the American Thoracic Society. 2023;20(4):539-547. doi:10.1513/​AnnalsATS.202206-524OC. PMID:36442147
• 7.

  O’Sullivan KJ, Collins L, McGrath D, Linnane B, O’Sullivan L, Dunne CP. Oscillating Positive Expiratory Pressure Therapy May Be Performed Poorly by Children With Cystic Fibrosis. Respiratory Care. 2019;64(4):398-405. doi:10.4187/​respcare.06329
• 8.

  Nyilas S, Bauman G, Pusterla O, Sommer G, Singer F, Stranzinger E, et al. Structural and Functional Lung Impairment in Primary Ciliary Dyskinesia. Assessment with Magnetic Resonance Imaging and Multiple Breath Washout in Comparison to Spirometry. Ann Am Thorac Soc. 2018;15(12):1434-1442. doi:10.1513/​AnnalsATS.201712-967OC
• 9.

  Kinghorn B, McNamara S, Genatossio A, Sullivan E, Siegel M, Bauer I, et al. Comparison of Multiple Breath Washout and Spirometry in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis and Healthy Controls. Annals of the American Thoracic Society. 2020;17(9):1085-1093. doi:10.1513/​AnnalsATS.201905-375OC. PMID:32603187
• 10.

  Zafar A, Hall M. In children with primary ciliary dyskinesia, which type of lung function test is the earliest determinant of decline in lung health: A systematic review. Pediatric Pulmonology. 2023;58(2):475-483. doi:10.1002/​ppul.26213
• 11.

  Green K, Buchvald FF, Marthin JK, Hanel B, Gustafsson PM, Nielsen KG. Ventilation inhomogeneity in children with primary ciliary dyskinesia. Thorax. 2012;67(1):49-53. doi:10.1136/​thoraxjnl-2011-200726
• 12.

  Vandervoort B, De Beuckeleer D, Huenaerts E, Schulte M, Vermeulen F, Proesmans M, et al. The Short Term Influence of Chest Physiotherapy on Lung Function Parameters in Children With Cystic Fibrosis and Primary Ciliary Dyskinesia. Front Pediatr. 2022;10:858410. doi:10.3389/​fped.2022.858410. PMID:35676908
• 13.

  Marques A, Bruton A, Barney A. Clinically useful outcome measures for physiotherapy airway clearance techniques: a review. Physical Therapy Reviews. 2006;11(4):299-307. doi:10.1179/​108331906X163441
• 14.

  Lauwers E, Ides K, Van Hoorenbeeck K, Verhulst S. Outcome measures for airway clearance techniques in children with chronic obstructive lung diseases: a systematic review. Respiratory Research. 2020;21(1):1-16. doi:10.1186/​s12931-020-01484-z. PMID:32807200
• 15.

  Barraza JAM, Benardis CNS, Jeria RSA, Sepúlveda DHA, Díaz IS, Navarrete PJB. Concordance in Discriminating Recordings of Different Lung Sounds Between Physiotherapists. Respiratory Care. 2020;65(2):177-182. doi:10.4187/​respcare.06624
• 16.

  Brooks D, Thomas J. Interrater reliability of auscultation of breath sounds among physical therapists. Physical therapy. 1995;75(12):1082-1088. doi:10.1093/​ptj/​75.12.1082
• 17.

  Whalley S, McManus I. Living with primary ciliary dyskinesia: a prospective qualitative study of knowledge sharing, symptom concealment, embarrassment, mistrust, and stigma. BMC Pulmonary Medicine. 2006;6(1). doi:10.1186/​1471-2466-6-25. PMID:17040569
• 18.

  Cheng L, Dong Y, Liu S. Anesthetic Management of Patients With Kartagener Syndrome: A Systematic Review of 99 Cases. J Cardiothorac Vasc Anesth. 2023;37(6):1021-1025. doi:10.1053/​j.jvca.2023.01.033
• 19.

  Schofield LM, Singh SJ, Yousaf Z, Wild JM, Hind D. Personalising airway clearance in chronic suppurative lung diseases: a scoping review. ERJ Open Research. Published online 2023:00010-02023. doi:10.1183/​23120541.00010-2023. PMID:37342087
• 20.

  Jain K, Padley S, Goldstraw E, Kidd S, Hogg C, Biggart E, et al. Primary ciliary dyskinesia in the paediatric population: range and severity of radiological findings in a cohort of patients receiving tertiary care. Clinical radiology. 2007;62(10):986-993. doi:10.1016/​j.crad.2007.04.015
• 21.

  Kennedy M, Noone P, Leigh M, Zariwala M, Minnix S, Knowles M, et al. High resolution CT of patients with primary ciliary dyskinesia. American Journal of Roentgenology. 2007;188(5):1232-1238. doi:10.2214/​AJR.06.0965
• 22.

  Cohen-Cymberknoh M, Simanovsky N, Hiller N, Hillel A, Shoseyov D, Kerem E. Differences in disease expression between primary ciliary dyskinesia and cystic fibrosis with and without pancreatic insufficiency. Chest. 2014;145(5):738-744. doi:10.1378/​chest.13-1162
• 23.

  Santamaria F, Montella S, Tiddens H, Guidi G, Casotti V, Maglione M, et al. Structural and functional lung disease in primary ciliary dyskinesia. Chest. 2008;134(2):351-357. doi:10.1378/​chest.07-2812
• 24.

  McIlwaine M, Bradley J, Elborn JS, Moran F. Personalising airway clearance in chronic lung disease. European Respiratory Review. 2017;26(143). doi:10.1183/​16000617.0086-2016. PMID:28223396
• 25.

  Lupton-Smith AR, Argent AC, Rimensberger PC, Morrow BM. Challenging a paradigm: Positional changes in ventilation distribution are highly variable in healthy infants and children. Pediatric Pulmonology. 2014;49(8):764-771. doi:10.1002/​ppul.22893
• 26.

  Fink JB. Positioning versus postural drainage. Respiratory care. 2002;47(7):769-777.
• 27.

  Gremmo M, Guenza M. Positive expiratory pressure in the physiotherapeutic management of primary ciliary dyskinesia in paediatric age. Monaldi archives for chest disease. 1999;54(3):255-257.
• 28.

  McCarren B, Alison JA. Physiological effects of vibration in subjects with cystic fibrosis. European Respiratory Journal. 2006;27(6):1204-1209. doi:10.1183/​09031936.06.00083605
• 29.

  Manor E, Gur M, Geffen Y, Bentur L. Cleaning and infection control of airway clearance devices used by CF patients. Chronic respiratory disease. 2017;14(4):370-376. doi:10.1177/​1479972317707652. PMID:28513198
• 30.

  Linnane B, O’Connell NH, Obande E, Dunne SS, Clancy C, Kiernan M, et al. Assessment of the microbial load of airway clearance devices used by a cohort of children with cystic fibrosis. Infection Prevention in Practice. 2021;3(3):100153. doi:10.1016/​j.infpip.2021.100153. PMID:34647008
• 31.

  Elkins MR, Bye PT. Mechanisms and applications of hypertonic saline. Journal of the Royal Society of Medicine. 2011;104(1_suppl):2-5. doi:10.1258/​JRSM.2011.S11101
• 32.

  Shapiro AJ, Zariwala MA, Ferkol T, Davis SD, Sagel SD, Dell SD, et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatric pulmonology. 2016;51(2):115-132. doi:10.1002/​ppul.23304. PMID:26418604
• 33.

  Housley G, Sanghani N, Bush A. P84 Longer term tolerability of nebulised hypertonic saline in children with respiratory disease. Published online 2017. doi:10.1136/​thoraxjnl-2017-210983.226
• 34.

  Kellett F, Robert NM. Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis. Respiratory medicine. 2011;105(12):1831-1835. doi:10.1016/​j.rmed.2011.07.019
• 35.

  NHS England specialised commissioning team. Clinical Commissioning Policy: Dornase alfa inhaled therapy for primary ciliary dyskinesia (all ages). NHS England. 2016. https:/​/​www.england.nhs.uk/​wp-content/​uploads/​2018/​07/​Dornase-alfa-inhaled-therapy-for-primary-ciliary-dyskinesia-all-ages.pdf
• 36.

  Asthma + Lung UK. How to use your inhaler. Asthma + Lung UK. 2025. Accessed May 22, 2025. https:/​/​www.asthmaandlung.org.uk/​living-with/​inhaler-videos
• 37.

  Lam YT, Papon JF, Alexandru M, Anagiotos A, Armengot M, Boon M, et al. Sinonasal disease among patients with primary ciliary dyskinesia: an international study. ERJ Open Research. 2023;9(3). doi:10.1183/​23120541.00701-2022. PMID:37228283
• 38.

  Pappa AK, Sullivan KM, Lopez EM, Adams KN, Zanation AM, Ebert CS Jr, et al. Sinus development and pneumatization in a primary ciliary dyskinesia cohort. American journal of rhinology & allergy. 2021;35(1):72-76. doi:10.1177/​1945892420933175. PMID:32551925
• 39.

  Rubbo B, Lucas JS. Clinical care for primary ciliary dyskinesia: current challenges and future directions. European Respiratory Review. 2017;26(145). doi:10.1183/​16000617.0023-2017. PMID:28877972
• 40.

  Møller ME, Alanin MC, Grønhøj C, Aanœs K, Høiby N, von Buchwaldm C. Sinus bacteriology in patients with cystic fibrosis or primary ciliary dyskinesia: A systematic review. American Journal of Rhinology & Allergy. 2017;31(5):293-298. doi:10.2500/​ajra.2017.31.4461. PMID:28859703
• 41.

  Alanin MC. Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia: adressing the paranasal sinuses. Dan Med J. 2017;64(5):B5361.
• 42.

  Mantovani RP, Sandri A, Boaretti M, Burlacchini G, Vigni VL, Scarazzai M, et al. Longitudinal monitoring of sinonasal and oral bacterial reservoirs to prevent chronic lung infection in people with cystic fibrosis. ERJ Open Research. 2020;6(3). doi:10.1183/​23120541.00115-2020. PMID:32864382
• 43.

  Lee S, Fernandez J, Mirjalili SA, Kirkpatrick J. Pediatric paranasal sinuses—Development, growth, pathology, & functional endoscopic sinus surgery. Clinical Anatomy. 2022;35(6):745-761. doi:10.1002/​ca.23888. PMID:35437820
• 44.

  Chitsuthipakorn WK, Hoang D, Seresirikachorn MP, Snidvongs K, K K. Optimal device and regimen of nasal saline treatment for sinonasal diseases: systematic review. OTO open. 2022;6(2). doi:10.1177/​2473974X221105277. PMID:35720767
• 45.

  Siddiqui ZT, Gupta M, Nam A, Rachmanidou RHK, The A. The management of paediatric rhinosinusitis. International Journal of Pediatric Otorhinolaryngology. 2021;147:110786. doi:10.1016/​j.ijporl.2021.110786
• 46.

  Park DY, Choi JH, Kim DK, Jung YG, Mun SJ, Min HJ, et al. Clinical practice guideline: nasal irrigation for chronic rhinosinusitis in adults. Clinical and Experimental Otorhinolaryngology. 2022;15(1):5-23. doi:10.21053/​ceo.2021.00654. PMID:35158420
• 47.

  Elgamal Z, Singh P, Geraghty P. The upper airway microbiota, environmental exposures, inflammation, and disease. Medicina. 2021;57(8):823. doi:10.3390/​medicina57080823. PMID:34441029
• 48.

  Simsek S, Inal-Ince D, Cakmak A, Emiralioglu N, Calik-Kutukcu E, Saglam M, et al. Reduced anaerobic and aerobic performance in children with primary ciliary dyskinesia. European journal of pediatrics. 2018;177:765-773. doi:10.1007/​s00431-018-3121-2
• 49.

  Fırat M, Boşnak-Güçlü M, Şişmanlar-Eyüboğlu T, Aslan AT. Aerobic exercise capacity, cough strength, posture, and depression in primary ciliary dyskinesia. Pediatric Pulmonology. 2023;58(1):73-80. doi:10.1002/​ppul.26158
• 50.

  Valerio G, Giallauria F, Montella S, Vaino N, Vigorito C, Mirra V, et al. Cardiopulmonary assessment in primary ciliary dyskinesia. European journal of clinical investigation. 2012;42(6):617-622. doi:10.1111/​j.1365-2362.2011.02626.x
• 51.

  NHS. Physical activity guidelines for children and young people. 2024. Accessed May 22, 2025. https:/​/​www.nhs.uk/​live-well/​exercise/​exercise-guidelines/​physical-activity-guidelines-children-and-young-people/​
• 52.

  NHS. Physical activity guidelines for children (under 5 years). 2022. Accessed May 22, 2025. https:/​/​www.nhs.uk/​live-well/​exercise/​physical-activity-guidelines-children-under-five-years/​
• 53.

  Dwyer TJ, Alison JA, McKeough ZJ, Daviskas E, Bye PTP. Effects of exercise on respiratory flow and sputum properties in patients with cystic fibrosis. Chest. 2011;139(4):870-877. doi:10.1378/​chest.10-1158
• 54.

  Heinz KD, Walsh A, Southern KW, Johnstone Z, Regan KH. Exercise versus airway clearance techniques for people with cystic fibrosis. Cochrane Database Syst Rev. 2022;6:CD013285. doi:10.1002/​14651858.CD013285.pub2. PMID:35731672
• 55.

  Pritchard A, Burns P, Correia J, Jamieson P, Moxon P, Purvis J, et al. ARTP statement on cardiopulmonary exercise testing 2021. BMJ open respiratory research. 2021;8(1):e001121. doi:10.1136/​bmjresp-2021-001121. PMID:34782330
• 56.

  Keenan V, Wilkins H, Friend A, Harris A. Continence Assessment in Paediatric Patients with Primary Ciliary Dyskinesia. European Respiratory Society; 2018. doi:10.1183/​13993003.congress-2018.PA1477
• 57.

  Goutaki M, Hüsler L, Lam YT, Koppe HM, Jung A, Lazor R, et al. Respiratory symptoms of Swiss people with primary ciliary dyskinesia. ERJ open research. 2022;8(2). doi:10.1183/​23120541.00673-2021. PMID:35415187
• 58.

  Dodd ME, Langman H. Urinary incontinence in cystic fibrosis. Journal of the Royal Society of Medicine. 2005;98(Suppl 45):28.
• 59.

  Massery M. Musculoskeletal and neuromuscular interventions: a physical approach to cystic fibrosis. Journal of the Royal society of Medicine. 2005;98(Suppl 45):55.
• 60.

  Frayman KB, Kazmerski TM, Sawyer SM. A systematic review of the prevalence and impact of urinary incontinence in cystic fibrosis. Respirology (Carlton, Vic). 2018;23(1):46-54. doi:10.1111/​resp.13125
• 61.

  Mateen A, Mustansar A, Mahmood S, Latif W, L T. Frequency of Musculoskeletal Disorders in Non-Cystic Fibrosis Bronchiectasis Patients: Cross Sectional Study. Pakistan journal of medical and health sciences. 2021;9:2345-2346. doi:10.53350/​pjmhs211592345
• 62.

  Simpson J, Nagakumar P, Narayanan M, Kang R, Kenia P. Musculoskeletal (MSK) assessment in children and young people (CYP) with Primary Ciliary Dyskinesia (PCD). European Respiratory Society. Published online 2022:2062. doi:10.1183/​13993003.congress-2022.2062
• 63.

  Barbato A, Frischer T, Kuehni C, Snijders D, Azevedo I, Baktai G, et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. European Respiratory Journal. 2009;34(6):1264-1276. doi:10.1183/​09031936.00176608
• 64.

  Fein VM, Schlegtendal C, Denz A, Koerner-Rettberg R, Brinkmann C, Risk F. Risk factors for the deterioration of pulmonary function in primary ciliary dyskinesia. Pediatric Pulmonology. 2023;58(7):195-198. doi:10.1002/​ppul.26417
• 65.

  Osterberg L, Blaschke T. Adherence to medication. New England Journal of Medicine. 2005;353(5):487-497. doi:10.1056/​NEJMra050100
• 66.

  Dixon E, Puckey M, Collins N, Marsh G, Pabary R. Striving for perfection, accepting the reality: A reflection on adherence to airway clearance and inhalation therapy for paediatric patients with chronic suppurative lung disease. Paediatric Respiratory Reviews. 2020;34:46-52. doi:10.1016/​j.prrv.2019.04.002
• 67.

  Wildman MOC, Maguire A, Arden C, et al. Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial. Thorax. 2022;77(5):461-469. doi:10.1136/​thoraxjnl-2021-217594. PMID:34556552