Topic 6.1. Reduced pulmonary function and pulmonary infection
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
Topic Contents
6.1 Reduced pulmonary function and pulmonary infection
6.1.1 The effects of Friedreich ataxia on pulmonary function
6.1.2 Monitoring pulmonary function
6.1.3 Management of reduced pulmonary function and preventing pulmonary infection
Disclaimer / Intended Use / Funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.
6.1 Reduced pulmonary function and pulmonary infection
Sub Subramony and Katherine Mathews
6.1.1 The effects of Friedreich ataxia on pulmonary function
There are no large-scale published data on pulmonary function tests in Friedreich ataxia (FRDA). Bulbar dysfunction and muscle weakness (related to upper motor neuron pathology) do occur in FRDA and may lead to restrictive lung disease. Neuromuscular restrictive lung disease typically leads to nocturnal hypoventilation causing sleep disturbance and abnormal nocturnal blood gases, with deleterious effects. Nocturnal problems may be compounded by the occurrence of obstructive sleep apnea. In a small unpublished observational study, close to 20% of participants with FRDA had one or more abnormal pulmonary function test (PFT) values, usually in those with more advanced FRDA (Corti, Smith & Subramony, unpublished data).
Other neuromuscular disorders such as Duchenne muscular dystrophy and amyotrophic lateral sclerosis, in which some data exist and care guidelines have been developed, are not strictly comparable due to greater degree of muscle strength loss in these illnesses; nevertheless, these can serve as models for the care of individuals with FRDA (1-4).
6.1.2 Monitoring pulmonary function
Monitoring for reduced pulmonary function should be done at least annually in Individuals with FRDA with advanced disease (i.e., non-ambulatory; or earlier if symptoms of sleep disordered breathing are elicited) during clinic visits.
Monitoring at clinic visits should include the following:
● Administer a neuro-respiratory checklist including questions about orthopnea, dyspnea during ordinary daytime activities, apnea during the night, poor sleep quality during the night, morning headache, decreased attention and concentration during the daytime, excess daytime sleepiness, excessive fatigue and repeated chest infections (5)
● Administer a sleepiness questionnaire (e.g., Epworth sleepiness scale) and a fatigue scale
● Assess respiratory excursions and cough strength during physical examination
● In individuals with advanced FRDA, perform tests for different respiratory muscle groups at least annually, including:
○ Spirometry: measure forced vital capacity (FVC) sitting and supine. A significant decline in supine FVC reflects diaphragmatic dysfunction
○ Other PFT measures such as lung volumes and maximal respiratory pressures
○ Peak expiratory cough flow (PECF)
○ Pulse oximetry and end tidal CO2 or transcutaneous pCO2
○ Polysomnography with capnography if obstructive sleep apnea or nocturnal hypoventilation is suspected based on above clinic based assessments.
6.1.3 Management of reduced pulmonary function and preventing pulmonary infection
- ● Consider chest physiotherapy and respiratory strength training. This may be more useful in the event of an acute intervening medical issue such as lung infection or surgery.
- ● For help with airway clearance, manual assisted coughing or mechanical insufflation-exsufflation (MI-E) is recommended if FVC < 50% predicted or PECF < 270 L/min or when maximum expiratory pressure is < 60 cm H2 Individual titration of MI-E is recommended.
- ● Initiate nocturnal assisted non-invasive ventilation (NIV) if any of the following indications exist: FVC < 50% predicted; maximum inspiratory pressure < 60 cm H2O; nocturnal hypercarbia (pCO2 > 50 mm Hg for ≥ 2% of sleep time or a 10 mm Hg increase in pCO2 compared to awake baseline pCO2 for ≥ 2% of sleep time); nocturnal hypoxia (SpO2 ≤ 88% for ≥ 2% of sleep time or 5 minutes continuously); or apnea-hypopnea index ≥ 5. Daytime hypoventilation indicated by hypercarbia of > 45 mm Hg or baseline PO2 < 95% on room air is also an indication for nocturnal assisted ventilation.
- ● Individuals with advanced FRDA and their caregivers should be educated regarding the risk of respiratory complications including higher risk of severe infections and the role of impaired airway clearance.
- ● Risk of pneumonia can be reduced for those with more severe FRDA through appropriate vaccinations for bacterial and viral infections (such as pneumovax and annual flu vaccines) and “social distancing” strategies when in contact with others.
Monitoring
QUESTION: Should monitoring for restrictive lung disease/sleep disordered breathing/sleep apnea versus no monitoring be used for people with Friedreich ataxia?
LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We conditionally recommend that individuals with advanced Friedreich ataxia be monitored* at least annually for restrictive lung disease and sleep disordered breathing (SDB).
*Monitoring should include a respiratory symptom check list (dyspnea, orthopnea, episodes of apnea during night, poor sleep, morning headache, decreased concentration and attention, fatigue, treated chest infection within the past few months), a sleepiness questionnaire and a fatigue scale. Annual (or more frequent) pulmonary function testing should be performed to include forced vital capacity (FVC), maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), peak expiratory cough flow (PECF), SpO2 and partial pressure of end tidal CO2 (PetCO2).
JUSTIFICATION: There are no published data. Expert opinion and limited unpublished data suggest that restrictive lung disease and SDB can occur in advanced Friedreich ataxia. Monitoring will be of benefit. Methods for monitoring include using a respiratory symptom check list (5), sleepiness and fatigue scales and pulmonary function tests.
Restrictive lung disease and SDB can lead to abnormal blood gases and symptoms that impair quality of life. Detecting these and providing appropriate intervention will be of benefit.
SUBGROUP CONSIDERATION: Monitoring is recommended for individuals with Friedreich ataxia with advanced disease.
Evidence to Recommendation Table PDFMonitoring at diagnosis
QUESTION: Should monitoring for restrictive lung disease/sleep disordered breathing/sleep apnea at diagnosis versus monitoring at later stages be used for people with Friedreich ataxia?
LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We conditionally recommend against monitoring for restrictive lung disease and sleep disordered breathing at diagnosis of Friedreich ataxia rather than at later stages of the disease, as there is no evidence that this would be of benefit.
JUSTIFICATION: There are no published data on prevalence of abnormal respiratory muscle function in Friedreich ataxia. Unpublished data indicates that restrictive lung disease and impaired cough can occur in later stages of the disease. There is no clear evidence of the effect of monitoring for restrictive lung disease/SDB/sleep apnea at diagnosis compared to later in the disease, on abnormal lung volumes; impaired airway clearance; excessive daytime sleepiness, or fatigue in individuals with Friedreich ataxia. Monitoring could be done in later stages of Friedreich ataxia.
SUBGROUP CONSIDERATION: Individuals who are later in the progression of Friedreich ataxia are more likely to experience restrictive lung disease.
Evidence to Recommendation Table PDFAssisted coughing
QUESTION: Should assisted coughing (mechanical/manual) versus no intervention be used for impaired airway clearance in Friedreich ataxia?
LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: In individuals with Friedreich ataxia and impaired airway clearance (PECF < 270 L/min or FVC < 50% predicted), we suggest assisted coughing (mechanical/manual) be implemented to assist in airway clearance and reduce the prevalence of chest infections.
JUSTIFICATION: Poor cough mechanisms likely occur in some individuals with advanced Friedreich ataxia. There are no major studies that address assisted coughing interventions in Friedreich ataxia. A patient survey suggests that this is an important problem and Friedreich ataxia experts seem to agree. One of the authors has unpublished data indicating impaired cough flow occurs in advanced Friedreich ataxia.
It may be conjectured that improved clearance of secretions will likely reduce probability of chest infections. Chest infection is second to cardiac disease as a cause of mortality in Friedreich ataxia (6).
SUBGROUP CONSIDERATION: This intervention should be considered for individuals with Friedreich ataxia who are non-ambulatory and have impaired cough flow and/or reduced forced vital capacity.
Evidence to Recommendation Table PDFChest physiotherapy
QUESTION: Should chest physiotherapy versus no intervention be used for people with respiratory weakness and restrictive lung disease with Friedreich ataxia?
LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: In people with respiratory weakness and restrictive lung disease with Friedreich ataxia, we conditionally recommend chest physiotherapy to improve respiratory function, reduce prevalence of chest infection, reduce dyspnea and improve airway clearance function.
JUSTIFICATION: There are no published data on restrictive lung disease and interventions in Friedreich ataxia. A patient survey and unpublished data from one of the authors indicate that this occurs in some patients with advanced Friedreich ataxia. A survey of experts suggests that chest physiotherapy provides benefit for respiratory function, chest infections, and airway clearance.
SUBGROUP CONSIDERATION: This recommendation is for people with Friedreich ataxia with respiratory weakness and restrictive lung disease. Chest physiotherapy may be particularly useful in the event of an acute superimposed medical issue such as surgery or chest infection.
Evidence to Recommendation Table PDFNon-invasive assisted ventilation
QUESTION: Should non-invasive ventilation versus no intervention be used for restrictive lung disease in Friedreich ataxia?
LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We conditionally recommend non-invasive assisted ventilation for patients with Friedreich ataxia and documented restrictive lung disease meeting the following thresholds: FVC < 50% predicted; maximum inspiratory pressure < 60 cm H2O; nocturnal hypercarbia (pCO2 > 50 mm Hg for ≥ 2% of sleep time or a 10 mm Hg increase in pCO2 compared to awake baseline pCO2 for ≥ 2% of sleep time); nocturnal hypoxia (SpO2 ≤ 88% for ≥ 2% of sleep time or 5 minutes continuously); or apnea-hypopnea index ≥ 5. Daytime hypoventilation indicated by hypercarbia of > 45 mm Hg or baseline PO2 < 95% on room air is also an indication for nocturnal assisted ventilation.
JUSTIFICATION: Restrictive lung disease can lead to abnormal blood gases with deleterious effects on cardiopulmonary health and also lead to symptoms that impair quality of life, both during the daytime and during sleep. There is no data on the use of non-invasive assisted ventilation in patients with Friedreich ataxia. This recommendation is based on limited data from similar disorders and expert guidelines in such disorders.
SUBGROUP CONSIDERATION: This recommendation is for individuals with advanced Friedreich ataxia and abnormal pulmonary function.
Evidence to Recommendation Table PDFRespiratory strength training
QUESTION: Should respiratory strength training versus no intervention be used for people with respiratory weakness and restrictive lung disease with Friedreich ataxia?
LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We cannot recommend either respiratory strength training or no respiratory strength training for people with Friedreich ataxia and respiratory weakness and restrictive lung disease. We suggest that in selected patients with respiratory weakness, supervised respiratory training be considered with monitoring of respiratory parameters and for adverse effects such as exhaustion.
JUSTIFICATION: Respiratory weakness can lead to symptoms of sleep disordered breathing such as fatigue, excessive daytime sleepiness and dyspnea and nocturnal abnormalities in blood gases with deleterious effects. However, there are no published data regarding monitoring methods or respiratory strength training in Friedreich ataxia. Based on limited low-level evidence in small studies and meta-analysis in some similar disorders, there is little objective evidence for respiratory strength training as an intervention for respiratory weakness (7, 8). However, Friedreich ataxia expert opinion suggests that respiratory strength training may be considered for individuals with later stage Friedreich ataxia with impaired pulmonary function tests indicating respiratory weakness.
SUBGROUP CONSIDERATION: This intervention could be considered for individuals with later stage Friedreich ataxia with impaired pulmonary function tests indicating respiratory weakness.
Evidence to Recommendation Table PDFLay summary of clinical recommendations for reduced pulmonary function & preventing pulmonary infection in Friedreich ataxia
Why these recommendations?
There are no good quality studies looking at the effects of Friedreich ataxia on breathing or possible treatments. However, the limited research available suggests that breathing problems can happen in patients who are in the later stages of the disease. Experience from other similar (but not identical) neuromuscular disorders suggests that although breathing changes may happen in Friedreich ataxia, breathing may be less affected than in the other disorders. This is due to muscle weakness not being as severe in Friedreich ataxia.
Weakness of breathing muscles may involve both the muscles that work to make air flow into the lungs (inspiratory muscles) and those that expel air from the lungs (expiratory muscles). Less capacity to pull air in can lead to “stiffening” of lung tissue and chest muscles (reduced compliance). This can lead to the collapse of the air pockets in the lungs (atelectasis), thereby making the problem worse. Spinal curvature (common in Friedreich ataxia) can also affect breathing function.
Impaired breathing can lead to reduction in oxygen levels in blood and tissues (oxygen desaturation) and increases in carbon dioxide levels (hypercarbia), both of which may cause problems and symptoms: these include poor sleep and daytime sleepiness, headache, fatigue and shortness of breath. If expiratory muscles are weakened, coughing is less effective, and the ability to clear fluids from lungs is reduced. This can lead to lung infections.
We suggest that monitoring for breathing problems in individuals with Friedreich ataxia once they are not ambulatory could be helpful.
Monitoring may include:
- asking about daytime symptoms such as sleepiness, fatigue, headache in the morning, and episodes of chest infection since the last clinic visit
- paying attention to chest motion and cough effectiveness during a physical examination
- lung function tests, including tests to evaluate cough and to measure lung volumes. These should be done at least yearly, or when symptoms happen.
- Other tests that could be useful include measuring oxygen and carbon dioxide levels in the blood using non-invasive techniques.
- An overnight sleep study may also be useful in selected individuals to see if respiratory weakness causes problems during sleep.
If these tests point to the need, interventions may be recommended, including:
- assisted coughing methods
- use of devices such as biPAP or AVAPS to increase air entry into the lungs and normalize blood oxygen and carbon dioxide levels
- respiratory strength training.
Individuals with Friedreich ataxia and impaired lung function may find it difficult to tolerate some of these interventions.
Individuals with more severe Friedreich ataxia can exercise “respiratory infection prevention strategies”. These include vaccinations for bacterial and viral infections and “social distancing” strategies when in contact with others. This recommendation is based on the experience of Friedreich ataxia experts and limited data from other similar disorders, as there is little direct evidence for infection prevention strategies in Friedreich ataxia.
What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
It may be important for you to discuss possible difficulty with breathing with your care providers and encourage good communication between members of your care team, including your neurologist, pulmonary or sleep specialist, physical therapist and primary care physician.
Who are these recommendations specifically for?
These recommendations are relevant for individuals with Friedreich ataxia who have more advanced disease or are experiencing breathing and/or sleep problems.
Professor, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Email: katherine-mathews@uiowa.edu
Sub H. Subramony, MD
Professor of Neurology and Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA
Email: s.subramony@neurology.ufl.edu
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These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.