W Goh, SL Lee, A Yung, WC Chow, V Wong

Abstract

Duchenne muscular dystrophy (DMD) is one of the major phenotype of dystrophinopathy. In typical cases of DMD, the strength of the lower limbs gradually deteriorate and majority become wheelchair bound by 12 years old. Weakness of respiratory muscles begin with decreasing functional ability and would die of respiratory failure or superimposed chest infection at late teens. Pulmonary rehabilitation had been reported to improve quality of life and prolonged life span in this group of patients. We studied respiratory function of 13 wheelchair bound DMD patients and assessed their attitude towards assisted ventilation. All the patients were found to have restrictive type of respiratory function with reduced peak flow rate. One patient was found to have type 2 respiratory failure. Assisted nocturnal ventilation via facial mask (Bi-PAP) was prescribed and his blood gases returned to normal during both day and night. His quality of life was improved. Despite the physical limitation in this group of patients, all of them showed willingness to use respiratory support to improve their respiratory function.

Introduction

Duchenne muscular dystrophy (DMD) is one of the major phenotype of Dystrophinopathy. Dystrophin is encoded by a large gene on the X-chromosome at Xp21. The clinical spectrum of dystrophinopathy includes Becker muscular dystrophy, muscle cramps and myalgia, limb girdle weakness, cardiomyopathy, asymptomatic raised serum creatine kinase and symptomatic carrier. In typical cases of DMD, children usually present with delay walking or frequent falls between 3 to 6 years. The strength of the lower limbs gradually deteriorate between 6 to 11 years and the majority become wheelchair bound by 12 years old. They usually die at their late teens due to respiratory failure¹ or superimposed chest infection. Inkley et al (1974)² noted a deterioration in pulmonary function begin even before they become wheelchair bound. Rideau et al (1981)³ reported respiratory function in Duchenne muscular dystrophy was characterized by a restrictive syndrome which severely impaired pulmonary function.

Pulmonary rehabilitation with assisted ventilation had been reported to improve quality of life and prolonged life span in this group of patients.^4-5 Smith et al (1987)⁶ highlighted the importance of treatment in respiratory deficit for patients with DMD. These treatment include weight control, deep-breathing exercise,⁷ assisted coughing, correction of scoliosis, treatment for chest infection and assisted ventilation. Patients with neuromuscular disease were reported to have associated nocturnal obstructive sleep apneas.^8-9 Sleep-related respiratory disturbances were frequently present with Duchenne muscular dystrophy¹⁰ and the effects of nocturnal hypoventilation were corrected by using nocturnal nasal positive pressure ventilation.^11-13

In Hong Kong SAR, the Paediatricians who treated children with DMD had adopted a 'non-active' approach due to perception of poor quality of life and limited resources. However, the outlook on life satisfaction of individual with DMD using mechanical ventilation had been reported to be very positive.^14,15 Bach et al reported that vast majority of the severely disabled chronic ventilator-assisted individuals with DMD had a positive affect. They were satisfied with life despite the physical dependence which precludes many of the activities most commonly associated with perceived quality of life for the physically able individuals.

Pulmonary care of patients with DMD in Hong Kong SAR was mainly confined to regular deep breathing exercises, postural drainage, assisted coughing and correction of scoliosis. Regular monitoring of lung function and the used of mechanical assisted ventilation was not part of the practice among Paediatricians in Hong Kong.

The purpose of our study were:

1. to review the respiratory status of our wheelchair bound DMD patients with a view to plan for a pulmonary rehabilitation programme and
2. to survey these patients' attitude towards assisted mechanical ventilation.

Materials and Methods

All the surviving wheelchair bound DMD patients that were seen at The Duchess of Kent Child Assessment Centre from 1987 to 1996 were included in the study. There were altogether 17 male patients, 3 had refused to be enrolled into the study. One child had moderate learning disability and was not able to cooperate with the study procedure and was excluded from study.

Day symptoms related to respiratory insufficiency were assessed by asking for history of sleep pattern during nighttime, morning headache, daytime somnolence, snoring during sleep and difficulty in clearing secretion. Bulbar function was assessed by asking for history of difficulty in swallowing and weak voice.

A survey on patient's attitude towards assisted home ventilation were performed by using questionnaire with the following questions:

1. Do you want to improve your respiratory function if something can be done?
2. Would you accept the use of facial mask with assisted ventilation?
3. If facial mask were inadequate in maintaining adequate lung function, would you accept tracheotomy?
4. Do you have any fearful feelings towards respirator?

Functional ability were assessed and classified according to Inkley's functional classification:²

1 - walks & climbs stairs without assistance

2, 3 - walks & climbs stairs with rail/aid

4 - walks unassisted & rises from chair

5 - walks unassisted, cannot rise from chair

6 - walks only with assistance/long brace independent

7 - walks with long brace & assistance

8 - stand in long brace, unable to walk

9 - wheelchair bound, limited activity

Lung function of each patient was evaluated by spirometry to document forced vital capacity (FVC) and forced expiratory volume (FEV 1). Each patient was asked to perform three times on the spirometry for supine and erect position, and the best recorded value was chosen for interpretation. Blood gases and blood haematocrit were taken to document hypoxemia or hypercapnea. Electrocardiogram, chest X-ray, heart rate, respiratory rate, and chest expansion were recorded to assessed cardiorespiratory function. Measurements on body height and arm-span for those who were wheelchair bound were taken for the reading of predicted FVC for normal Hong Kong children. FVC values of study subjects were compared with normal Hong Kong children to assess the percentage of decline.

Result

Altogether there were 13 male patients. Their age ranged between 12 to 24 years (Mean 16.8). Duration of wheelchair bound ranged between 0.7 years to 9 years with a mean duration of 5 years. Among 13 patients, 10 were in functional class 9 and 3 were in functional class 8. The degree of muscular weakness was so severe that most of them needed the assistance of other family member to turn their posture at least twice during sleep. However, about 77% (n=10) felt that they were able to sleep well during the night. About 60% (n=8) admitted having difficulty in clearing secretion especially during episodes of upper respiratory tract infection. Day sleepiness and headache occurred in 23% (n=3) (Table I). Among these 3 who had day symptom one was detected to have type 2 respiratory failure on blood gases and the other one was detected to have carbon dioxide retention during early morning blood gases sampling. Symptoms of bulbar weakness were present in 23% (n=3).

Clinical signs on examination of the respiratory system were as follows (Table I): The mean respiratory rate and heart rate were faster than average and chest expansion was reduced. All 13 patients had scoliosis and 3 had been operated. One patient had abdominal squeeze which indicated respiratory difficulty was later found to have type 2 respiratory failure. About half of them were detected to have weakness in neck flexion which is a common feature during late stage of the disease.

All the patients were found to have restrictive type of respiratory function with reduced FVC and FEV1 values (Fig 1). FVC of DMD patients were 1.25 ± 0.4 (range 0.51 to 1.9 litres). The predicted FVC of height compatible normal Hong Kong male were 2.93 ± 0.5 (range 2.14 to 3.83 litres). Therefore the percentage of FVC of DMD patients when compared to the Hong Kong standard was 44.5% x± 18 (range 17% to 79%)(Fig 2). The FEV1 values were also reduced when compared to the normal population (range 18.6% to 78%)(Fig 3). The FVC/FEV1 ratio for DMD was all within normal range. These findings were compatible with restrictive respiratory pattern without airway obstruction.

We compared the different values % FVC with their blood gases result to see if any value could be identified to indicate a significant respiratory decline. There were 5 patients (31%) who had % FVC below 40 and 6 patients (46%) had % FVC between 40 to 70% and 2 patients (23%) had % FVC above 70%. Patients who had % FVC<40 was found to have a lower oxygen saturation, higher PaCO2 and lower PaO2 of blood oxygen. P value using unpaired t test were statistically significant (P value=0.015) for PaO2 values (Table II). P values for PaCO2 and O2 saturation were not significant. However, these blood gases values were taken during daytime and therefore it would not accurately reflect nocturnal hypoventilation. Sleep study with nocturnal oxygen saturation monitoring with early morning blood gases should be performed for patients with % FVC below 40.

The oxygen saturation from arterial blood gases ranged from 92.6 to 98.9 (Mean 97.5 ± 1.7) with mean PaO2 of 13.7 ± 2.2 (range 9.5 to 16.69) and mean PaCO2 of 4.9 ± 0.8 (range 4.2 to 7.4). One patient was found to have type 2 respiratory failure with PaCO2 at 7.4 and PaO2 was 9.5 in arterial blood gases. He had hourly desaturation during sleep and his early morning blood gases showed low PaO2 and carbon dioxide retention with compensated metabolic alkalosis. Assisted nocturnal nasal intermittent positive pressure ventilation with Bi-level positive airway pressure (Bi-PAP) was prescribed and his blood gases returned to normal during both day and night.

Fig. 1 Comparing FVC of DMD and HK Standard

Fig. 2 Percentage FVC of DMD compared to HK Standard

Fig. 3 Comparing FEV1 of DMD and HK Standard

Survey on patient's willingness to use assisted ventilation to improve lung function showed a very positive response. All of the 13 patients (100%) indicated willingness to use nasal mask as a means of assisted ventilation. However when they were asked about tracheostomy 4 (31%) indicated willingness to have it done if necessary and 3 (23%) were uncertain about the procedure. Another 6 (46%) of them indicated not to have the procedure if it is required. Among these 6 patients 5 of them indicated a feeling of fear and uncertainty towards the use of respirator.

Discussions

Progressive deterioration in lung function of patients with DMD was related to scoliosis, weak cough, thoracic mechanical abnormality, microatelectasis with reduced lung compliance, ventilation perfusion imbalance and sleep related hypoxemia. Three stages of decline had been identified¹⁶ these were difficulty in clearing secretions with microatelectasis, nocturnal hypoventilation and daytime hypoxemia.

Our patients had been identified to have all the three stages of respiratory decline. Among 13 DMD, 8 (61.5%) admitted having difficulty in clearing secretion during episodes of upper respiratory tract infection. Difficulty in clearing secretions will eventually lead to microatelectasis. Nocturnal hypoventilation had been identified in two patients and one of them had daytime hypoxemia as well.

The patient was an 18-year-old young man who enjoyed study and did well in his school performance. We knew very well that if no intervention were given to correct the respiratory failure, the patient would be dead very soon. The institution of nocturnal Bi-PAP corrects the blood gases to normal both day and night. The patient reported improvement in daytime somnolence and was able to concentrate and enjoy his study once again. Another patient who had daytime headache was found to have high carbon dioxide in early morning blood gases after nocturnal sleep monitoring. Nocturnal CPAP would correct abnormal blood gases and improved day symptom.

The patient who needed assisted mechanical ventilation had % FVC of 18% and FEV1 of 18.6%. It is important therefore to have regular lung function assessment to detect respiratory function decline and to institute appropriate treatment for pulmonary rehabilitation. This group of patients would be followed up 6 monthly at the Pulmonary Rehabilitation clinic. Measurements on FVC/FEV1 with arterial blood gases will be taken to assess lung volume and gases exchange. Those patients who were detected to have % FVC at 40 or below or having day symptom of hypoxemia would be admitted for nocturnal sleep monitoring. Patients with DMD who are still ambulatory would also be followed up regularly at 6 monthly interval on lung function.

Support from the family is very important for pulmonary rehabilitation to be successful. The financial implication in the purchase and maintenance of the ventilator needed to be explained to the parents at the beginning. The Hospital Authority of Hong Kong had not provided additional funding for home ventilator purchase. However there are other charitable organization, e.g. the Samaritan fund provides funding for such purpose. The higher disability allowance for the handicapped person could also be a source of funding for rental of home ventilator.

Another important area of support from the family would be the actual physical care of the ventilator. The patients would not be able to put on the face mask and would need the help of their family member to put on the face mask for them as well as adjusting the ventilator setting. This could be an extra stress to the family when the use of ventilator is unfamiliar.

The quality of life for patients with DMD was studied by our clinical psychologist while our study was in progress. The purpose of her study was to explore the Health-Related Quality of life (HRQOL) in DMD patients.¹⁷ She concluded that 'DMD patients in this study have the health related quality of life relatively well reserved despite their highly dependent life pattern.¹ Her conclusion had further supported our belief in the pulmonary rehabilitation program to provide good quality of life and maintain life support for DMD before they reached their terminal stage of the disease.

The quality of life for patients with DMD had been neglected over the past few years. The use of assisted ventilation at night had improved quality of life in one of our patients as well as prolonged his life span. DMD is still incurable; it must not be regarded as untreatable. Assisted ventilation may be warranted if their functional abilities suggest they have not reached terminal phase of their illness. Daytime respiratory performance can be improved by nocturnal assistance alone. Cardiac disease may be made worse by pulmonary hypertension, hypoxemia, and hypercapnia; assisted ventilation may be beneficial in both respiratory and cardiac failure.

We suggest that pulmonary rehabilitation should be an integral part of the treatment for our patients with Duchenne Muscular dystrophy. It is important to monitor their lung function when their physical ability begins to decline. The use of assisted ventilation at the right time may improve quality of life and prolong their life span.

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