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Respiratory failure and related pulmonary complications in
individuals with some neuromuscular diseases (NMD) are well
known. Lung complications, especially in the late stages of
some diseases, not only result in a decreased quality of life
and increased burden on the family, but also develop a vicious
cycle and contribute significantly to death. Therefore, intervention
measures successful in preventing and reducing the pulmonary
complications should be of benefit in preserving physical
capacity, quality of life, and a longer life span.
Pathogenesis
of Impaired Pulmonary Function in NMDs: There
are two types of lung disease. Obstructive lung disease affects
the lung itself as in asthma and emphysema. Restrictive lung
disease, occurring in disorders with muscle weakness, spine
deformity and obesity, is caused by weakness of the muscles
of respiration. There are two parts to normal respiration,
inspiration and expiration. The major inspiratory muscle is
the diaphragm, while the most active expiratory muscles are
the abdominal and external intercostal (chest) muscles.
Impaired respiratory function may be due to altered control
of respiration by the brain, anterior horn cells of the spinal
cord, or the phrenic nerve, as well as weak muscles, skeletal
deformity and obesity. Weakness of the diaphragm leads to
reduced inspiratory pressure, low lung volumes and impaired
gas exchange, whereas weakness of the intercostal and abdominal
muscles results in an ineffective cough and inability to adequately
clear secretions. Involvement of the muscles of the pharynx
leads to failure to protect the airway resulting in aspiration
pneumonia.
In addition to predisposing the individual to pneumonia, longstanding
respiratory muscle weakness may lead to diffuse microatelectasis
as well as ventilation perfusion imbalance. These result in
a greater hypoxic state and increase mortality and morbidity.
In advanced stages, many individuals with neuromuscular diseases
(NMDs) develop malnutrition and anemia secondary to gastrointestinal
dysfunction, poor appetite, and bowel movement disorders.
Anemia not only results in fatigue and weakness of the respiratory
muscles but also causes tissue deoxygenation.
Monitoring the respiratory function of individuals with NMD
is critical to proper management. The most important is patient
and physician awareness of the signs and symptoms of possible
respiratory difficulty: prolonged and frequent respiratory
tract infections, (especially pneumonia), shortness of breath
(with ambulation, at rest, and during sleep), dyspnea, and
respiratory compromise requiring assisted ventilation.
Laboratory tests include spirometric pulmonary function tests
(PFT), measurements of static airway pressures (maximum inspiratory
and expiratory mouth pressures), and evaluation of arterial
blood gases. The most frequently used PFT is forced vital
capacity (FVC). FVC is the single most important measurement
for following the natural history of a disease or response
to treatment. It also closely reflects the degree of general
pulmonary function and appears to offer an accurate prognostic
index. Measurement of maximum inspiratory (MIP) and expiratory
(MEP) pressures will detect abnormalities of acute or chronic
respiratory muscle weakness at an early stage.
Restrictive lung disease, secondary to weakness of the respiratory
muscles and often compounded by spine deformity, occurs in
most NMDs. There is, however, marked variation in the severity
and clinical importance. The primary factors determining the
severity are the degree of weakness, the rate of progression
of the weakness, and the presence of spine deformity. (See
Feature on spine deformity.)
While individual differences occur within a disease, RLD is
usually only severe in amyotrophic lateral sclerosis, Duchenne
muscular dystrophy and spinal muscular atrophy Types I and
II. Using the American Medical Association guidelines, severe
RLD is defined as FVC below 50% predicted, moderate RLD between
51-60% predicted, and mild RLD between 61-80% predicted. A
normal FVC is defined as 80% or more of the predicted value.
Usually, low FVCs are associated with low static airway pressures,
especially MEP.
Airway pressures are expressed as a percentage of the lower
limit of the normal predicted range so any value below 100%
is abnormal. In all NMDs, MEP is more abnormal than MIP indicating
greater weakness of the expiratory muscles. This is fortunate
because a reduced MEP would seldom be a cause of respiratory
failure (if the inspiratory muscles are adequate), since expiration
is primarily a passive action. Diseases with very low FVCs
and static airway pressures frequently have a high percent
of pulmonary complication such as pneumonia.
The results regarding specific diseases in this review were
based on data obtained during a ten-year RRTC study.
Spinal Muscular Atrophy
(SMA): SMA Type II is an early onset disease in which
the onset usually becomes apparent in the first 6-18 months
of life. While less severe than SMA Type I (Werdnig-Hoffman
disease), it is still associated with significant morbidity
and mortality. The average age of the individuals in the RTC
study was 17 years. The average FVC for 17 individuals was
54 ± 26 percent of the predicted value. Forty one percent
had severe RLD, 17% moderate RLD, and 12% mild RLD. There
was a significant disease duration effect but no spine deformity
effect. Forty-seven percent had a history of significant respiratory
complications, and both disease duration and FVC had an effect
on the frequency of complications. There was no effect of
spine deformity. Using both FVC and pulmonary complications
as a criteria, there were significant pulmonary problems in
47%, with 21% requiring mechanical ventilatory assistance.
SMA Type III (Kugelberg-Welander disease) is a chronic, later
onset disorder (5-15 years old) with low morbidity and mortality.
The average age of the individuals in this study was 40 years.
The average FVC for 13 individuals was 84 ± 22 percent of
predicted value. Only one individual had severe RLD, 7% moderate
RLD and 21% mild RLD. There was no disease duration effect.
Only two individuals had a history of pulmonary complications.
In both SMA Type II and III individuals, even in those with
normal FVCs, MIP and especially MEP were reduced. MIP was
71 ± 18% of the percent predicted and MEP only 45 ± 16% with
a disease duration effect.
Duchenne Muscular
Dystrophy (DMD): The average age of the individuals
in the RTC study was 12 years. While FVC showed a marked variation
with age, the average FVC for 80 individuals was 47 ± 31 percent
of the predicted value. Thirty-five percent had severe RLD,
4% moderate RLD, and 27% mild RLD. Disease duration had a
profound effect on FVC, especially in the second decade of
life. While there was a linear decline from age 5 years, the
greatest decline occurred between 10 and 20 years of age.
Between ages 7 to 10, the average rate of decline was only
0.3% per year, while between 10 to 20 years it was 8.5% per
year. After age 20 years, the decline slowed slightly to 6.2%
per year. While spine deformity and ambulatory status also
affected FVC, disease duration was the major factor.
The average percent predicted MIP was 23 ± 12 and the MEP
13 ± 9 for all individuals. Maximum static pressures as a
percent of predicted values were decreased early in the course
of the disease between 5 to 10 years of age as compared to
percent predicted FVC which remained relatively stable.
Thirty-four percent had a history of significant respiratory
complications with a marked increase in rate of complications
with age; 7% ages 3-8, 17% ages 9-14, 48% ages 15-20, and
68% in ages 21 and above. There was a strong relationship
between pulmonary complications and percent predicted FVC,
and individuals with spine deformity had a higher frequency
of complications than those without. However, scoliosis and
pulmonary complications both increased with age.
Amyotrophic
Lateral Sclerosis (ALS): The average age of the
individuals in this RTC study was 60 ± 13 years, and the average
FVC for 42 subjects was 61 ± 25% of the predicted value. Twenty-one
percent had severe RLD, 17% moderate RLD, and 21% mild RLD.
MIP was 47 ± 29 and MEP 27 ± 15 of percent predicted. There
was a rapid decrease in pulmonary function within 2 to 3 years
of diagnosis. Fifty-eight percent had a history of significant
respiratory complications and the frequency increased with
disease duration; 15% one year duration, 23% two years duration,
and 62% three or more years duration. Complications and pulmonary
function were also significantly related; the lower the FVC,
the greater the percent of complications.
Hereditary
Spinal Cerebellar Ataxia (HSCA): The average
age of the individuals in this RTC study was 37 ± 16 years,
and the average FVC for 19 subjects was 73 ± 20% of the predicted
value. Twenty-one percent had severe RLD, 10% moderate RLD
and 21% mild RLD. MIP was 65 ± 19 and MEP 37 ±
14 of percent predicted. Thirty-seven percent had a history
of significant respiratory complications. While the frequency
of complications was slightly greater in individuals with
a disease duration longer than 20 years, there was no relationship
between predicted FVC and the percent of complications, and
no spine deformity effect on pulmonary function or complications.
Myotonic Muscular
Dystrophy (MMD): Two types of MMD are recognized;
congenital MMD (C-MMD) and noncongenital MMD. In C-MMD, onset
is at birth, and there is delayed motor development and abnormal
intellectual capacity. The average age of the individuals
in the RTC study was 14 years, and the average FVC for 10
individuals was 72 ± 12% of the predicted value. Twenty percent
had severe RLD, 40% moderate RLD, and 30% mild RLD. There
was a spine deformity effect on FVC but no age or disease
duration effect. The average predicted MIP was 29 ± 15% and
the MEP 20 ± 9% with no spine deformity or disease duration
effect. Twenty-four percent had a history of respiratory complications,
all in individuals with spine deformity. Disease duration
did not affect the frequency of complications and there was
no correlation with FVC levels.
In MMD, the average age of the individuals in this study was
37 years, and the average FVC for 57 individuals was 75 ±
19% of predicted value. Fourteen percent had severe RLD, 5%
moderate RLD, and 38% mild RLD. There was a disease duration
and age effect, and the decrease in FVC was related to the
frequency of the pulmonary complications. The MIP was 51 ±
20 and MEP 27 ± 10 of percent predicted, with a disease duration
effect. Twenty-six percent had a history of respiratory complications.
While there was no overall disease duration effect, 70% of
the individuals with severe RLD had pulmonary complications
as compared to only 14% in those with normal FVCs. There was
no spine deformity effect on pulmonary complications or function,
since spine deformity was rare or mild when present.
Congenital Myopathy:
The average age of the individuals with congenital muscular
dystrophy was 9 years, and the average FVC for 6 subjects
was 80 ± 28% of the predicted value. Fifteen percent had severe
RLD and 30% mild RLD. Twenty-eight percent had a history of
significant pulmonary complications.
The average age of the individuals with other types of congenital
myopathies was 18 years, and the average FVC for 8 subjects
was 83 ± 12% of the predicted value. None had severe or moderate
RLD or pulmonary complications.
There was no age, disease duration, or spine deformity effect,
and no correlation between pulmonary function and complications.
Becker's Muscular Dystrophy
(BMD): The average age of the individuals in this
RTC study was 26 years, and the average FVC for 13 individuals
was 83 ± 26% of the predicted value. Fourteen percent had
severe RLD, and 14% mild RLD. All individuals with FVC less
than 8% were 30 years of age or older. MIP was 75 ± 15 and
MEP 73 ± 15 of percent predicted, with a greater age decline
in MEP. Only two individuals (13%) had a history of significant
respiratory complications. There was no disease duration effect
and no correlation of disease duration with the pulmonary
function measurements. There was no spine deformity effect
on pulmonary complications or function.
Facioscapulohumeral
Dystrophy (FSHD): The average age of the individuals
in this RTC study was 38 years, and the average FVC for 23
individuals was 81 ± 22% of the predicted value. Thirteen
percent had severe RLD, 4% moderate RLD, and 30% mild RLD.
There was no age or disease duration effect. Although there
was a significant difference in FVC between those with and
without spine deformity, this difference is of doubtful clinical
importance since 53% of the individuals had normal FVCs, and
there was no correlation with the frequency of pulmonary complications.
MIP was 75 ± 24 and MEP 43 ± 18 of percent predicted, with
no disease duration, age, or spine deformity effect. Twenty
two percent had a history of significant pulmonary complications,
and there was no disease duration, age, or spine deformity
effect on the complications.
Limb Girdle Syndrome
(LGS): There are five types of LGS including the
three types reviewed in this RTC study. The autosomal recessive
muscular dystrophy of childhood (ARMDC) has an age of onset
between 4 to 15 years, predominantly proximal weakness, and
a relatively rapid progression in some cases. The average
age of the individuals with ARMDC was 42 years, and the average
FVC for 13 individuals was 81 ± 23% of the predicted value.
Only one subject had severe RLD, two had moderate RLD, and
four (31%) had mild RLD. Thirty one percent had a history
of significant respiratory complications.
The autosomal dominant late onset (ADLO) LGS has an onset
in adult life or late adolescence, proximal weakness, and
slow progression. The average age of individuals with the
ADLO type of LGS was 50 years, and the average FVC for 7 subjects
was 74 ± 37% of the predicted value. Only one individual had
severe RLD and one had mild RLD. Fifteen percent had a history
of pulmonary complications.
The pelvifemoral (PF) LGS has a variable onset and hereditary
pattern, slow progression, and predominantly lower extremity
weakness. The average age of individuals with this type of
LGS was 43 years, and the average FVC for 11 subjects was
82 ± 21% of the predicted value. One individual had severe
RLD and 5 (45%) had mild RLD. Fifteen percent had a history
of pulmonary complications.
In all types of LGS, MIP was 79 ± 34 and MEP 44 ± 16 of percent
predicted. There was no age, disease duration or spine deformity
effect on any of the pulmonary function measurements or pulmonary
complications. However, pulmonary complications occurred in
83% of the individuals with severe RLD as compared to only
21% in those with normal pulmonary function.
Hereditary
Motor Sensory Neuropathy (HMSN, Charcot-Marie-Tooth syndrome):
The average age of the individuals in this RTC study was 44
years, and the average FVC for 40 individuals was 92 ± 22%
of the predicted value. Only one subject had severe RLD, 7%
moderate RLD, and 20% mild RLD. There was no disease duration,
age, or spine deformity effect, and no correlation with the
frequency of pulmonary complications. MIP was 101 ± 37 and
MEP 57 ± 20 of percent predicted with no disease duration,
age or spine deformity effect. Only 14% had a history of significant
respiratory complications. Although phrenic nerve (nerve
to diaphragm) conduction was markedly abnormal, there was
no significant correlation between pulmonary function measurements,
clinical symptoms and nerve conduction.
Management of RLD:
Overall, goals of pulmonary care in NMDs are: 1) maintenance
of respiratory homeostasis, 2) effective use of respiratory
muscles, and 3) prevention of lung infections. Long term objectives
are to lead as active and comfortable a life as possible and
to prolong life.
The major emphasis in early intervention pulmonary rehabilitation
is to prevent and/or reverse the vicious cycle leading to
respiratory failure and includes: 1) educating patient and
family about the course of each NMD, and pulmonary hygiene
techniques, 2) nutrition instructions to prevent obesity and
malnutrition, 3) exercise and physical activity to improve
general endurance and avoid fatigue, 4) correction of spine
deformity, if present, and 5) encourage deep and slow respirations.
When muscle weakness becomes severe, glossopharyngeal breathing
techniques, pulmonary therapy (chest percussion, postural
drainage), respirator use, and oxygen supplementation may
be necessary. Each intervention item depends on the individual's
pulmonary condition.
Individuals with NMD easily develop lung infection. With the
use of antibioticss, infections can usually be controlled.
Prevention of infections is just as important as treatment,
and all individuals with NMD should receive Pneumovax and
yearly flu shots. It is also important to do postural drainage
if there is stagnation of secretions in the lungs.
Late intervention measures include body respirators and cuirass
ventilation. There are many types of positive and negative
pressure ventilation devices with both advantages and disadvantages.
Examples of the former are pneumobelts, nasal mask, mouth
mask or lipseal, and tracheostomy. Examples of the latter
are porta-lungs, cuirass devices and plastic wraps. Most authorities
favor negative-pressure ventilation devices. Individuals with
NMD usually need mechanical ventilation when: 1) FVC is less
than two times the predicted tidal volume, less than 1000
ml, or less than 15% predicted, 2) MIP is less than 20 cm
H2O, and 3) there is pneumonia especially with
a CO2 blood gas more than 50%. When oxygen supplement
is used, a mask-adaptive terminal piece is better than a nasal
cannulae in order to maintain a constant concentration of
inspired oxygen.
Exercise Activities:
The cardiopulmonary response of individuals with NMDs to exercise
has been shown not to be significantly different from able-bodied
subjects. The two types of exercise training used to improve
respiratory efficiency are nonspecific aerobic exercise (bicycle,
swimming) and specific respiratory muscle training. Aerobic
exercise does not increase vital capacity but may result in
a more efficient use of the respiratory muscles. Studies regarding
the effectiveness of specific respiratory therapy programs,
usually emphasizing inspiratory muscle resistive exercise
training, are conflicting. From these studies it would appear
that although respiratory muscle endurance (MIP and MEP) may
be slightly improved, other components of pulmonary function,
such as vital capacity, are not affected. Since individuals
with better initial respiratory reserve respond best to training,
the benefit to those with very weak muscles would be small.
Moreover, in advanced weakness, weak respiratory muscles are
working against reduced compliance of the lungs and chest
wall, and may be already close to a fatiguing threshold. In
this situation, added inspiratory resistance exercise could
then be potentially dangerous.
Summary.
Restrictive lung disease represents a common complication
in some types of NMDs especially in SMA, DMD and ALS. Pulmonary
intervention in these disorders is one part of the rehabilitation
process that can be very important. If individuals are free
of respiratory complications, their life span will be longer
and their quality of life enhanced.
From RRTC Newsletter, September 1994.
