what-when-how
In Depth Tutorials and Information
message of the pulmonary discussion is that more work
needs to be done in this area. Kaplan and colleagues
20
review their experience with a novel spino-thoracic fixa-
tion device, evaluated in four type III OI patients 8-12
years of age. All demonstrated improved pulmonary
function, arterial blood gases and mobility after an aver-
age of 24 months of follow-up. Scoliosis angles decreased
as much as 34 degrees.
LoMauro and colleagues
2
compared pulmonary func-
tion and thoracic geometry in OI patients classified as
type III (
n
= 7) or type IV (
n
= 15). The increased pulmo-
nary function impairment in type III patients compared
with type IV was directly correlated with the degree of
thoracic geometry abnormalities.
Radunovic and colleagues
21
reported on results in
99 individuals with OI compared with 52 controls with
respect to their right ventricular size and pulmonary arte-
rial dimensions. Most subjects had pulmonary function
testing and echocardiography performed and those with
OI were categorized based on clinical evaluation into
types I, III and IV. All RV dimensions and some PA mea-
sures were increased in OI patients compared with con-
trols and those measurements in OI type III patients were
larger than in type I, type IV and controls. Surprisingly,
there did not appear to be a correlation of these measure-
ments with severity of pulmonary function abnormality
or with degree of scoliosis. These last findings may be
related to the smaller sample sizes in these subgroups,
since the observations that were statistically significant in
the larger groupings were barely so (
p
<0.05).
Finally, and quite relevant to our growing under-
standing of the contribution of intrinsic pulmonary
parenchymal disease in OI, is the work of Thiele and col-
leagues.
22
They evaluated a mouse model of OI in detail
(Aga2) with respect to intrinsic cardiopulmonary dis-
ease. They found that this model demonstrated signifi-
cant loss of extracellular matrix integrity in the heart and
lungs. They correlated their murine findings in a cohort
of human OI patients in which a decline in pulmonary
function and increasing pulmonary restriction was found
to be independent of progression of skeletal abnormali-
ties such as scoliosis.
The future of our understanding of pulmonary dis-
ease in OI will depend on concerted careful follow-up
of lung function on a longitudinal basis, both as study
cohorts and to aid in clinical management. As bone
strengthening therapeutics are developed that directly
benefit people with OI, it is hoped that there will be
prevention of the major architectural abnormalities of
the chest bony structures. This should provide a major
improvement in the pulmonary and cardiac status of
those with OI.
Therapeutics based on the molecular biology or
genetics of OI hold potential to correct collagen and
other abnormalities associated with this condition and
prevent the need for the many therapies described in
this and other chapters of this topic.
Finally, a better, more direct understanding of how
the collagen defects in OI affect the connective tissue of
the lungs and heart is needed. Only with such an under-
standing can we evaluate completely the contribution of
connective tissue derangement in the chest to cardiopul-
monary disease in OI.
CONCLUSIONS
Lung disease in OI is a common, often progressive
problem. Common lung diseases in the general popula-
tion occur commonly in OI as well, although the effects
of such common lung diseases can be magnified in the
OI patient. While derangements in the bony architecture
of the chest are among the most visible of the pulmonary
problems in severe OI, there is likely a range of effects on
lung function due to abnormal collagen-rich lung con-
nective tissue, although the magnitude of these affects
remains poorly studied.
As with most people affected by a chronic pulmo-
nary problem, acute exacerbations, whether due to infec-
tion, asthma, COPD, fractures or other cause, should be
treated aggressively. Awareness of pulmonary disease
and its treatment will improve the quality of life of indi-
viduals with OI and, in many cases, extend the length of
life as well.
References
[10]
