**3. Results**

### **3.1 Demographic features of HMV patients group and MV inpatients**

#### **3.1.1 HMV patients group**

HMV patients group included 434 patients from 14 institutes. Gender was male: 356, female: 78. The number of representative disease were as follows; 262 patients with Duchenne muscular dystrophy, 60 myotonic dystrophy, 17 Becker muscular dystrophy, 16 limb-girdle muscular dystrophy, 14 spinal muscular atrophy, and so on (Table 1-1).


BMD, Becker muscular dystrophy; CMD, congenital muscular dystrophy; DMD, Duchenne muscular dystrophy; EDMD, Emery-Dreifuss muscular dystrophy; FCMD, Fukuyama congenital muscular dystrophy; FSHD, facio-scapulo-humeral muscular dystrophy; LGMD, limb-girdle muscular dystrophy; MD, Myotonic dystrophy; MG, myasthenia gravis; SMA, spinal muscular atrophy; SPMA, spinal progressive muscular atrophy, UCMD, Ullrich congenital muscular dystrophy

Table 1-1. Details of disease(HMV: from 14 institutes)

#### **3.1.2 MV inpatients group**

106 Neuromuscular Disorders

The data which we requested 27 institutes specializing muscular dystrophy care was as follows; the number of patients introduced HMV after 1999, diagnosis of disease, gender, age at being introduced HMV, type of mechanical ventilation, such as non-invasive positive pressure ventilation (NPPV) or tracheostomy intermittent ventilation (TIV), present status,

We selected data of newly MV introduced inpatients after 1999 from the database of the

HMV patients group included 434 patients from 14 institutes. Gender was male: 356, female: 78. The number of representative disease were as follows; 262 patients with Duchenne muscular dystrophy, 60 myotonic dystrophy, 17 Becker muscular dystrophy, 16 limb-girdle

BMD, Becker muscular dystrophy; CMD, congenital muscular dystrophy; DMD, Duchenne muscular dystrophy; EDMD, Emery-Dreifuss muscular dystrophy; FCMD, Fukuyama congenital muscular dystrophy; FSHD, facio-scapulo-humeral muscular dystrophy; LGMD, limb-girdle muscular dystrophy; MD, Myotonic dystrophy; MG, myasthenia gravis; SMA, spinal muscular atrophy; SPMA, spinal

progressive muscular atrophy, UCMD, Ullrich congenital muscular dystrophy

Table 1-1. Details of disease(HMV: from 14 institutes)

**2.2 Patients introduced HMV after 1999** 

muscular dystrophy wards.

**3.1.1 HMV patients group** 

**3. Results** 

death cause for death case, main caregiver, and so on.

**2.3 Patients introduced MV in muscular dystrophy wards after 1999** 

**3.1 Demographic features of HMV patients group and MV inpatients** 

muscular dystrophy, 14 spinal muscular atrophy, and so on (Table 1-1).

MV inpatients group included 915 inpatients. Gender was male: 718, female: 197. The number of representative disease were as follows; 476 Duchenne muscular dystrophy, 222 myotonic dystrophy, 35 Becker muscular dystrophy, 58 limb-girdle muscular dystrophy, 19 spinal muscular atrophy, and so on (Table 1-1).

#### **3.1.3 Mean age at starting mechanical ventilation and type of ventilation**

The range of mechanical ventilation introduction age for HMV patients was 6.3~72.8 years old (mean 25.9), and that of MV inpatients was 0.0~78.0 years old (mean 33.2). The number of NPPV introduction cases of HMV patients was 420, and that of MV inpatients was 517 (Table 1-2). Fifty of NPPV cases of HMV group were switched to tracheostomy during the course.


Table 1-2. Mean age at starting mechanical ventilation and type of ventilation

#### **3.2 Survival analysis of HMV patients group and MV inpatients**

We performed survival analysis of those two groups. The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death. Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,689 days, while that of inpatients was 2,988 days (Log Rank (Mantel-Cox) p<0.01) (Fig. 1).

Fig. 1. Comparison between HMV Patients and Mechanical Ventilation Inpatients (Total) Endpoint for HMV patient: death or transition to hospitalization Endpoint for MV inpatient: death

Comparison Between Courses of Home and Inpatients

(Duchenne muscular dystrophy )

Endpoint for MV inpatient: death

**with myotonic dystrophy** 

(myotonic dystrophy )

(Table 5).

Mechanical Ventilation in Patients with Muscular Dystrophy in Japan 109

Fig. 2. Comparison between HMV Patients and Mechanical Ventilation Inpatients

**3.3.4 Mean age at starting mechanical ventilation and type of ventilation of patients** 

Table 4. Mean age at starting mechanical ventilation and type of mechanical ventilation

The trend of nutrition was similar to Duchenne muscular dystrophy. The number who required tube feeding in MV inpatients group was apparently greater than HMV group

Mean age at starting mechanical ventilation of myotonic dystrophy was 46.8 years old, ranged from 15.8 to 72.8 years old. While that of inpatient with myotonic dystrophy was 50.6 years old, ranged from 12.0 to 76.0 years old. There was no significant difference between two groups. The number of NPPV introduction cases of HMV patients with myotonic dystrophy was 55, and that of TIV was 5. The number of NPPV case was greater than TIV. While the number of NPPV introduction cases of MV patients with myotonic dystrophy was 108, and that of TIV was 114. In MV patients with myotonic dystrophy, the

Endpoint for HMVpatient: death or transition to hospitalization

number and proportion of NPPV and TIV were almost equal (Table 4).

**3.3.5 Type of nutrition of patients with myotonic dystrophy** 

### **3.3 Analysis data of Duchenne muscular dystrophy and myotonic dystrophy**

As the number of patients with Duchenne muscular dystrophy and myotonic dystrophy was great in these two groups, we analyzed the data of Duchenne muscular dystrophy and myotonic dystrophy separately.

#### **3.3.1 Mean age at starting mechanical ventilation and type of ventilation of patients with Duchenne muscular dystrophy**

Mean age at starting mechanical ventilation of Duchenne muscular dystrophy was 19.8 years old, ranged from 11.5 to 39.9 years old. While that of inpatient with Duchenne muscular dystrophy was 21.5 years old, ranged from 10.0 to 42.0 years old. There was no significant difference. The number of NPPV introduction cases of HMV patients with Duchenne muscular dystrophy was 220, and that of MV inpatients was 338 (Table 2).


Table 2. Mean age at starting mechanical ventilation and type of mechanical ventilation (Duchenne muscular dystrophy )

#### **3.3.2 Type of nutrition of patients with Duchenne muscular dystrophy**

The number of patients who required tube feeding, including a nasal or oral nutrition tube, and undergoing a percutaneous endoscopic gastrostomy (PEG) was apparently greater in MV inpatients group than HMV group (Table 3).


Table 3. Type of nutrition (Duchenne muscular dystrophy )

#### **3.3.3 Survival analysis of two Duchenne muscular dystrophy groups**

We performed survival analysis of those two Duchenne muscular dystrophy groups. The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death. Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,562 days, while that of inpatients was 3,739 days (Log Rank (Mantel-Cox) p<0.01) (Fig. 2).

As the number of patients with Duchenne muscular dystrophy and myotonic dystrophy was great in these two groups, we analyzed the data of Duchenne muscular dystrophy and

**3.3.1 Mean age at starting mechanical ventilation and type of ventilation of patients** 

Duchenne muscular dystrophy was 220, and that of MV inpatients was 338 (Table 2).

Table 2. Mean age at starting mechanical ventilation and type of mechanical ventilation

The number of patients who required tube feeding, including a nasal or oral nutrition tube, and undergoing a percutaneous endoscopic gastrostomy (PEG) was apparently greater in

We performed survival analysis of those two Duchenne muscular dystrophy groups. The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death. Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,562 days, while that of inpatients was 3,739 days (Log Rank (Mantel-Cox) p<0.01)

**3.3.2 Type of nutrition of patients with Duchenne muscular dystrophy** 

Mean age at starting mechanical ventilation of Duchenne muscular dystrophy was 19.8 years old, ranged from 11.5 to 39.9 years old. While that of inpatient with Duchenne muscular dystrophy was 21.5 years old, ranged from 10.0 to 42.0 years old. There was no significant difference. The number of NPPV introduction cases of HMV patients with

**3.3 Analysis data of Duchenne muscular dystrophy and myotonic dystrophy** 

myotonic dystrophy separately.

(Duchenne muscular dystrophy )

(Fig. 2).

MV inpatients group than HMV group (Table 3).

Table 3. Type of nutrition (Duchenne muscular dystrophy )

**3.3.3 Survival analysis of two Duchenne muscular dystrophy groups** 

**with Duchenne muscular dystrophy** 

Fig. 2. Comparison between HMV Patients and Mechanical Ventilation Inpatients (Duchenne muscular dystrophy )

Endpoint for HMVpatient: death or transition to hospitalization Endpoint for MV inpatient: death

#### **3.3.4 Mean age at starting mechanical ventilation and type of ventilation of patients with myotonic dystrophy**

Mean age at starting mechanical ventilation of myotonic dystrophy was 46.8 years old, ranged from 15.8 to 72.8 years old. While that of inpatient with myotonic dystrophy was 50.6 years old, ranged from 12.0 to 76.0 years old. There was no significant difference between two groups. The number of NPPV introduction cases of HMV patients with myotonic dystrophy was 55, and that of TIV was 5. The number of NPPV case was greater than TIV. While the number of NPPV introduction cases of MV patients with myotonic dystrophy was 108, and that of TIV was 114. In MV patients with myotonic dystrophy, the number and proportion of NPPV and TIV were almost equal (Table 4).


Table 4. Mean age at starting mechanical ventilation and type of mechanical ventilation (myotonic dystrophy )

### **3.3.5 Type of nutrition of patients with myotonic dystrophy**

The trend of nutrition was similar to Duchenne muscular dystrophy. The number who required tube feeding in MV inpatients group was apparently greater than HMV group (Table 5).

Comparison Between Courses of Home and Inpatients

Table 6. Cause of death (Duchenne muscular dystrophy )

conspicuous in HMV group, accounting for 3/6(Table 7).

**3.4.2 Cause of death of myotonic dystrophy** 

Table 7. Cause of death (myotonic dystrophy )

and had an accidental case (Table 6).

Mechanical Ventilation in Patients with Muscular Dystrophy in Japan 111

The most frequent cause of death was heart related disorders, such as heart failure and arrhythmia, accounting for 16/29 for HMV group and 33/67 for MV inpatient group. Frequency was not significantly different between two groups. In MV inpatient group, respiratory related disorders, such as respiratory failure and respiratory infection, accounted for 23/67.HMV group included more sudden death cases than MV inpatient,

The majority of death case of myotonic dystrophy was reported from MV inpatient group. The most frequent cause was respiratory related disorders, such as respiratory tract infection and respiratory failure, which accounted for 29/56. Sudden death case was


Table 5. Type of nutrition (myotonic dystrophy )

Fig. 3. Comparison between HMV Patients and Mechanical Ventilation Inpatients (myotonic dystrophy )

Endpoint for HMVpatient: death or transition to hospitalization Endpoint for MV inpatient: death

#### **3.3.6 Survival analysis of two myotonic dystrophy groups**

Similarly, we performed survival analysis of those two myotonic dystrophy groups. The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death. Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,557 days, while that of inpatients was 1,972 days. There was no significance (Fig. 3).

#### **3.4 Death case**

The total number of death cases was 215 (Table 1-1). As the number of death case of Duchenne muscular dystrophy and myotonic dystrophy was the majority, we analyzed the data of Duchenne muscular dystrophy and myotonic dystrophy separately.

#### **3.4.1 Cause of death of Duchenne muscular dystrophy**

The number of death cases of HMV patients was 29, and that of MV inpatients was 67.

Fig. 3. Comparison between HMV Patients and Mechanical Ventilation Inpatients

Similarly, we performed survival analysis of those two myotonic dystrophy groups. The endpoint for HMV patients was death or transition to hospitalization, and that for MV inpatient was death. Kaplan-Meier analysis showed that 75% life time of HMV patients was 1,557 days, while that of inpatients was 1,972 days. There was no significance (Fig. 3).

The total number of death cases was 215 (Table 1-1). As the number of death case of Duchenne muscular dystrophy and myotonic dystrophy was the majority, we analyzed the

The number of death cases of HMV patients was 29, and that of MV inpatients was 67.

data of Duchenne muscular dystrophy and myotonic dystrophy separately.

Endpoint for HMVpatient: death or transition to hospitalization

**3.3.6 Survival analysis of two myotonic dystrophy groups** 

**3.4.1 Cause of death of Duchenne muscular dystrophy** 

Table 5. Type of nutrition (myotonic dystrophy )

(myotonic dystrophy )

**3.4 Death case** 

Endpoint for MV inpatient: death

The most frequent cause of death was heart related disorders, such as heart failure and arrhythmia, accounting for 16/29 for HMV group and 33/67 for MV inpatient group. Frequency was not significantly different between two groups. In MV inpatient group, respiratory related disorders, such as respiratory failure and respiratory infection, accounted for 23/67.HMV group included more sudden death cases than MV inpatient, and had an accidental case (Table 6).


Table 6. Cause of death (Duchenne muscular dystrophy )

### **3.4.2 Cause of death of myotonic dystrophy**

The majority of death case of myotonic dystrophy was reported from MV inpatient group. The most frequent cause was respiratory related disorders, such as respiratory tract infection and respiratory failure, which accounted for 29/56. Sudden death case was conspicuous in HMV group, accounting for 3/6(Table 7).


Table 7. Cause of death (myotonic dystrophy )

Comparison Between Courses of Home and Inpatients

HMV group was better than inpatient group.

ventilated patients have been getting back home.

patients (Windisch, 2008).

with obscure time-sequential analysis.

remarkable.

**4. Conclusion** 

(both Duchenne muscular dystrophy and myotonic dystrophy).

Mechanical Ventilation in Patients with Muscular Dystrophy in Japan 113

In Survival analysis, outcome of patients with Duchenne muscular dystrophy of MV inpatients group was better than HMV group. Meanwhile in that of myotonic dystrophy,

In MV inpatient group of Duchenne muscular dystrophy, respiratory related death was

Approximate 2500 beds for patients with muscular dystrophy and related disorders are now provided among 27 institutions in Japan. In accordance with progress in therapeutic strategies for respiratory failure (American Thoracic Society Documents, 2004) and heart failure (Ishikawa, 1999; Matsumura, 2010), the life span of patients with muscular dystrophy prolonged (Bushby 2010a, b). Now, most inpatients admitted to muscular dystrophy wards have severe general conditions and many are assisted by mechanical ventilation (Tatara,

In recent two decades, social welfare systems and home medical care systems in Japan have been changing gradually. HMV has been penetrating into home medical care (Joseph, 2007). The number of HMV patients has been increasing (Tatara, 2006). Stable mechanical

Our study demonstrated that the course of HMV patients was fairly good, although there was difference between Duchenne muscular dystrophy and myotonic dystrophy in long term outcome. However, the support system for patients and caregivers is not perfect. Our study also showed that burden of caregivers was supposed to be severe. The system for patients and caregivers should be adjusted (Dybwik, 2011). And safety net systems also

The muscular dystrophy wards may be requested to offer the circumstances for those who have difficulties in continuing HMV. There is necessarily needs for hospitalization of HMV

Study limitation: This study has limitation on bias of collecting patients' information. Specifically, information of HMV patients were reported from 14 institutes among 27 institutes, and MV inpatient information is the result of extraction from muscular dystrophy wards database. Extracted data from database has some ambiguous points in connection

In HMV group, some sudden death cases and accidental death case were conspicuous.

Caregivers of HMV group were constructed by patients' families, centrally mother.

2006; 2008), which is accordance with our data of MV patients in this study.

should be adjusted to avoid accidental event leading to patient's death.

**3.7 Summary of results of Duchenne muscular dystrophy and myotonic dystrophy**  Proportion of TIV was higher in MV inpatients group than HMV group. And proportion of tube feeding was also higher in MV inpatients group than HMV group. Namely, respiratory condition and nutritional status were more severe in MV inpatients group than HMV group

#### **3.5 Outcome of HMV patients and MV inpatients with Duchenne muscular dystrophy and myotonic dystrophy**

One hundred ninty four cases with Duchenne muscular dystrophy among 262 cases continued HMV, while 46 cases with myotonic dystrophy among 60 cases continued HMV (Table 8). Twenty two cases with Duchenne muscular dystrophy were switched to hospitalization.


Table 8. Outcome (Duchenne muscular dystrophy and myotonic dystrophy )

#### **3.6 Caregivers for HMV patients**

Caregivers for most of HMV patients with Duchenne muscular dystrophy were patients' families (Table 9). In particular, patients' mothers were playing important role in continuing HMV. Similarly, caregivers for HMV patients with myotonic dystrophy were patients' families. On reflecting their age, some caregivers were patient' spouse (Table 9).


Table 9. HMV-continuing cases main caregiver (Duchenne muscular dystrophy and myotonic dystrophy)

#### **3.7 Summary of results of Duchenne muscular dystrophy and myotonic dystrophy**

Proportion of TIV was higher in MV inpatients group than HMV group. And proportion of tube feeding was also higher in MV inpatients group than HMV group. Namely, respiratory condition and nutritional status were more severe in MV inpatients group than HMV group (both Duchenne muscular dystrophy and myotonic dystrophy).

In Survival analysis, outcome of patients with Duchenne muscular dystrophy of MV inpatients group was better than HMV group. Meanwhile in that of myotonic dystrophy, HMV group was better than inpatient group.

In MV inpatient group of Duchenne muscular dystrophy, respiratory related death was remarkable.

In HMV group, some sudden death cases and accidental death case were conspicuous.

Caregivers of HMV group were constructed by patients' families, centrally mother.
