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Upper airway obstruction during head flexion in morquio's disease
Upper Airway Obstruction During Head Flexion in Morquio’s Disease
MARC R. PRITZKER, M.D. RICHARD A. KING, M.D. RICHARD S. KRONENBERG,
M.D.
Minneapolis, Minnesota
Previous reports of pulmonary function in patients with Morquio’s disease have emphasized the restrictive nature of their ventilatory defect. We describe a patient in whom pulmonary disability was secondary to upper airway obstruction from collapse of the trachea during head flexion. The same phenomenon was demonstrated in one of two other patients with Morquio’s disease, both of whom were asymptomatic. Positionally dependent airway obstruction may be an important cause of pulmonary disability in Morquio’s disease. Morquio’s disease (mucopolysaccharidosis IV) is an inherited metabolic disorder characterized by excess keratan sulfate excretion in the urine and a distinctive clinical picture of short stature, spinal and chest wall deformities, cornea1 opacities and deafness. Previous reports of the pulmonary complications in Morquio’s disease have emphasized the importance of loss of lung volume secondary to thoracic cage deformity [l-3]. In this paper we describe a patient with Morquio’s disease in whom the major pulmonary complication was tracheal obstruction occurring during head flexion. Evidence of position-dependent upper airway obstruction was also found in one of two asymptomatic patients with Morquio’s disease. CASE REPORT A 25 year old white man presented to the Pulmonary Clinic in November 1978 complaining of dyspnea on exertion and decreasing exercise tolerance. His symptoms were more pronounced with the head held in a position of cervical flexion. There was no history of asthma, allergy, pneumonia, toxic exposure or smoking. Physical examination revealed the characteristic features of Morquio’s disease (Figure 1) In the chest breath sounds were present bilat-
erally, but airflow was markedly diminished with cervical flexion. After the suspicion of tracheal obstruction had been confirmed, two other patients with Morquio’s disease, both of whom wcrc asymptomatic, agreed to undergo noninvasive testing of their pulmonary function. All three patients underwent pulmonary function tests, including lung volumes, spirometry, flow-volume loops and plethysmography. performed with their heads in a normal resting position. Each test (except for plethysmography) was then repeated with the head in maximal flexion. In addition, in Patient 1 tracheal tomograms and fiberoptic tracheoscopy were performed in both head positions. For comparison, pulmonary function tests in normal and maximally flexed head positions were obtained in three normal, nonsmoking men. From the Department of Medicine, University of Minnesota Hospitals, Minneapolis, Minnesota. Requests for reprints should be addressed to Dr. Richard S. Kronenberg, Box 270, University of Minnesota Hospitals, Minneapolis, Minnesota 55455. Manuscript accepted July 12, 1979.
RESULTS Results of the pulmonary function tests in the three patients with Morquio’s disease are shown in Table I. All three demonstrated restrictive defects with reduced vital capacity and total lung capacity. In addition. Patients 1 and 2 demonstrated marked worsening of their
September 1980
The American Journal of Medicine
Volume 69
467
pulmonary function with their heads in flexion. This effect of head flexion was not seen in the normal subjects. The flow-volume loops in the one symptomatic patient (Patient 1)are shown in Figure 2. Some degree of upper airway obstruction was apparent with his head held in its normal position. With progressive head flexion increasingly severe upper airway obstruction developed until, with maximal head flexion, airway occlusion was almost complete. These findings were substantiated by tracheal tomography and by tracheoscopy. During flexion the trachea appeared almost completely occluded (Figure 3A), whereas at the same tomographic level, it was patent in the normal head position (Figure 3B). When the trachea was observed directly during head flexion the posterior wall of the trachea buckled anteriorly so that the tracheal lumen was reduced to a slit. COMMENTS
Figure 1. Profile of Patient 1. The patient has the typical physical features of Morquio’s disease with dwarfism and a short neck, The position of the patient’s neck (extension) is the one preferred by the patient for maximum breathing
comfort.
32-
3.2 k
Figure 2. Flow volume loops in Patient I showing the effect of increasing degrees of head flexion. The loop on the left was obtained with the patient’s head in its normal position (see Figure 1). The middle loop represents moderate head flexion and the loop on the right, full head flexion. The inner loops are normal or tidal breathing, and the outside loops are forced inspiratory and expiratory vital capacities.
466
September
1960 The American Journal of Medicine
In the family which formed the basis for Morquio’s original report, three of the four affected members died of “pulmonary complications” [4]. Subsequent reports detailing results of pulmonary function testing in patients with Morquio’s disease have shown a restrictive ventilatory defect similar to that seen in patients with kyphoscoliosis [l-3]. Each of the three patients in our study demonstrated moderate to severe lung disease. In addition, in two of our three patients flow volume loops showed evidence of position-dependent upper airway obstruction when the neck was held in flexion. In one patient tracheoscopy showed nearly total expiratory tracheal collapse with cervical flexion. Lateral films of the cervical spine and airway documented airway narrowing but failed to implicate the pathologic cervical spine motion to which these patients are prone [5]. Upper airway obstruction has been reported as a feature of Hurler’s syndrome [6] and is believed to be secondary to deposition of mucopolysaccharide material in the tissues comprising the upper airway [7,8]. The resultant distortion and rigidity would then account for anatomic disruption. In contrast to the rigidity induced ‘by tissue deposition of mucopolysaccharides in patients with Hurler’s syndrome, patients with Morquio’s disease demonstrate laxity of connective tissue structures similar to that seen in connective tissue disorders involving collagen, We postulate that the observed airway obstruction in patients with Morquio’s disease results from a combination of abnormal upper airway support related to the abnormalities of cartilage metabolism, and a relative redundancy of the trachea engendered by our patients’ short necks, and the position of cervical flexion. This may account for the characteristic way patients with Morquio’s disease hold their heads, a position of maximal extension (Figure 11. Clinicopathologic support for this hypothesis comes from patients with developmental
Volume 69
TABLE I
Effect of Head Position on Pulmonary Function Patient 2
Patient 1
FEV, (liters)
FVC (liters)
FEF25-75 (lkec) V50
FEVl%
RV (liters)
Patient 3 Normal
Flexed
Flexed
0.7-t
0.3
1.9
1.5
1.8
1.7
G
zi
G
G
G
3z
0.8
0.4
2.2
1.7
2.0
2.0
2.1
2.1
3.7
G
G
G
2.7
2.1
2.5
2.6
4.2
4.2
3.7
3.6
3.4
4.a
5.3
5.3
90%
85%
1.2
0.3
G
G
1.2
-0.41 6.3
4.0
G
4.8
88 %
75%
86%
88%
TLC (liters)
FRC (liters)
Normal
Flexed
Normal’
1.2
3.3
2.9
5.7
iiT
1.1
1.1
3.2
3.0
0.3
1.0
0.9
G
1.9
i7
NOTE: FEV, = forced expiratory volume in 1 second; FVC = forced vital capacity: FEF 25_rs = forced expiratory flow between 25 and 75 percent of the FVC; Vso = instantaneous flow rate at 50 percent of the FVC; FEV 1% = FEV,:FVC; TLC = total lung capacity; FRC = functional residual capacity; RV = residual volume. l The head position preferred by the patient. + Measured value Predicted value
Figure 3. Patient 1. Lateral tomograms of larynx and trachea. A, on the left the patient’s head is flexed. The arrows indicate the tracheal air column which is narrowed to a thin slit. B, on the right, the patient’s head is in its normal extended position. The tracheal air column (arrows) is now widely patent. Both tomographic cuts are at the same level. The air-filled esophagus can be seen posteriorly. September 1980
The American Journal of Medicine
Volume 89
489
UPPER AIRWAY OBSTRUCTION IN MORQUIO’S DISEASE-PRITZKER
tracheomalacia and obstructive pulmonary disease who have been shown to have tracheal collapse. Pathologic study of these patients has shown a deficiency in the absolute amount of cartilage, loss of cartilage rigidity and loss of elastic tissue [9]. Although histologic confirmation of abnormal tracheal cartilage was not considered to be warranted in our patients, the findings of tracheal obstruction and tracheal buckling during expiration are consistent with this pathogenesis. Tracheal or reconstructive surgery was considered for Patient 1; however, neck surgery in patients with Morquio’s disease is both technically difficult and
ET AL.
hazardous because of their marked spinal deformities [S]. After considering the surgical risks, the patient declined both tracheal reconstructive surgery and tracheostomy. In patients with Morquio’s disease, who demonstrate both spinal cord compression and tracheal collapse, simultaneous corrective surgery might be considered. ACKNOWLEDGMENT
We thank Dr. Robert J. Rotenberg for referring Patient and Dr. Gregory Grabowski for referring Patients 2 and 3. 1
REFERENCES 1.
2. 3. 4. 5.
470
Hope EOS:Some aspects of respiratory function in three siblings with Morquio-Bra&ford disease. Thorax 1969; 28: 335. Buhain W: Pulmonary function in Morquio’s disease: a study of two siblings. Chest 1977; 68: 41. Fraser RG, Pare ]A: Diagnosis of diseases of the chest, vol III, 2nd ed. Philadelphia: WB Saunders, 1979. McKusick VA: Heritable disorders of connective tissue, 4th ed. St. Louis: CV Mosby, 583: 1972. Kopits S: Orthopedic complications of dwarfism. Clinical
September 1980 The American Journal of Medicine
Orthop 1976: 114: 153. Murray 1: Pulmonary disability in the Hurler syndrome. N Engl J Med 1954; 261: 378. 7. Caffey J: Gargoylism: study of pathologic lesions and clinical review of 12 cases. Am J Dis Child 1948; 76: 239. 8. de Lange C: Some remarks on gargoylism. Acta Paediat Stand 1943-44; 31: 398-416. 9. Campbell A: Tracheobronchial collapse, a variety of obstructive respiratory disease. Br J Dis Chest 1963; 57: 174. 6.
Volume 89
MARC R. PRITZKER, M.D. RICHARD A. KING, M.D. RICHARD S. KRONENBERG,
M.D.
Minneapolis, Minnesota
Previous reports of pulmonary function in patients with Morquio’s disease have emphasized the restrictive nature of their ventilatory defect. We describe a patient in whom pulmonary disability was secondary to upper airway obstruction from collapse of the trachea during head flexion. The same phenomenon was demonstrated in one of two other patients with Morquio’s disease, both of whom were asymptomatic. Positionally dependent airway obstruction may be an important cause of pulmonary disability in Morquio’s disease. Morquio’s disease (mucopolysaccharidosis IV) is an inherited metabolic disorder characterized by excess keratan sulfate excretion in the urine and a distinctive clinical picture of short stature, spinal and chest wall deformities, cornea1 opacities and deafness. Previous reports of the pulmonary complications in Morquio’s disease have emphasized the importance of loss of lung volume secondary to thoracic cage deformity [l-3]. In this paper we describe a patient with Morquio’s disease in whom the major pulmonary complication was tracheal obstruction occurring during head flexion. Evidence of position-dependent upper airway obstruction was also found in one of two asymptomatic patients with Morquio’s disease. CASE REPORT A 25 year old white man presented to the Pulmonary Clinic in November 1978 complaining of dyspnea on exertion and decreasing exercise tolerance. His symptoms were more pronounced with the head held in a position of cervical flexion. There was no history of asthma, allergy, pneumonia, toxic exposure or smoking. Physical examination revealed the characteristic features of Morquio’s disease (Figure 1) In the chest breath sounds were present bilat-
erally, but airflow was markedly diminished with cervical flexion. After the suspicion of tracheal obstruction had been confirmed, two other patients with Morquio’s disease, both of whom wcrc asymptomatic, agreed to undergo noninvasive testing of their pulmonary function. All three patients underwent pulmonary function tests, including lung volumes, spirometry, flow-volume loops and plethysmography. performed with their heads in a normal resting position. Each test (except for plethysmography) was then repeated with the head in maximal flexion. In addition, in Patient 1 tracheal tomograms and fiberoptic tracheoscopy were performed in both head positions. For comparison, pulmonary function tests in normal and maximally flexed head positions were obtained in three normal, nonsmoking men. From the Department of Medicine, University of Minnesota Hospitals, Minneapolis, Minnesota. Requests for reprints should be addressed to Dr. Richard S. Kronenberg, Box 270, University of Minnesota Hospitals, Minneapolis, Minnesota 55455. Manuscript accepted July 12, 1979.
RESULTS Results of the pulmonary function tests in the three patients with Morquio’s disease are shown in Table I. All three demonstrated restrictive defects with reduced vital capacity and total lung capacity. In addition. Patients 1 and 2 demonstrated marked worsening of their
September 1980
The American Journal of Medicine
Volume 69
467
pulmonary function with their heads in flexion. This effect of head flexion was not seen in the normal subjects. The flow-volume loops in the one symptomatic patient (Patient 1)are shown in Figure 2. Some degree of upper airway obstruction was apparent with his head held in its normal position. With progressive head flexion increasingly severe upper airway obstruction developed until, with maximal head flexion, airway occlusion was almost complete. These findings were substantiated by tracheal tomography and by tracheoscopy. During flexion the trachea appeared almost completely occluded (Figure 3A), whereas at the same tomographic level, it was patent in the normal head position (Figure 3B). When the trachea was observed directly during head flexion the posterior wall of the trachea buckled anteriorly so that the tracheal lumen was reduced to a slit. COMMENTS
Figure 1. Profile of Patient 1. The patient has the typical physical features of Morquio’s disease with dwarfism and a short neck, The position of the patient’s neck (extension) is the one preferred by the patient for maximum breathing
comfort.
32-
3.2 k
Figure 2. Flow volume loops in Patient I showing the effect of increasing degrees of head flexion. The loop on the left was obtained with the patient’s head in its normal position (see Figure 1). The middle loop represents moderate head flexion and the loop on the right, full head flexion. The inner loops are normal or tidal breathing, and the outside loops are forced inspiratory and expiratory vital capacities.
466
September
1960 The American Journal of Medicine
In the family which formed the basis for Morquio’s original report, three of the four affected members died of “pulmonary complications” [4]. Subsequent reports detailing results of pulmonary function testing in patients with Morquio’s disease have shown a restrictive ventilatory defect similar to that seen in patients with kyphoscoliosis [l-3]. Each of the three patients in our study demonstrated moderate to severe lung disease. In addition, in two of our three patients flow volume loops showed evidence of position-dependent upper airway obstruction when the neck was held in flexion. In one patient tracheoscopy showed nearly total expiratory tracheal collapse with cervical flexion. Lateral films of the cervical spine and airway documented airway narrowing but failed to implicate the pathologic cervical spine motion to which these patients are prone [5]. Upper airway obstruction has been reported as a feature of Hurler’s syndrome [6] and is believed to be secondary to deposition of mucopolysaccharide material in the tissues comprising the upper airway [7,8]. The resultant distortion and rigidity would then account for anatomic disruption. In contrast to the rigidity induced ‘by tissue deposition of mucopolysaccharides in patients with Hurler’s syndrome, patients with Morquio’s disease demonstrate laxity of connective tissue structures similar to that seen in connective tissue disorders involving collagen, We postulate that the observed airway obstruction in patients with Morquio’s disease results from a combination of abnormal upper airway support related to the abnormalities of cartilage metabolism, and a relative redundancy of the trachea engendered by our patients’ short necks, and the position of cervical flexion. This may account for the characteristic way patients with Morquio’s disease hold their heads, a position of maximal extension (Figure 11. Clinicopathologic support for this hypothesis comes from patients with developmental
Volume 69
TABLE I
Effect of Head Position on Pulmonary Function Patient 2
Patient 1
FEV, (liters)
FVC (liters)
FEF25-75 (lkec) V50
FEVl%
RV (liters)
Patient 3 Normal
Flexed
Flexed
0.7-t
0.3
1.9
1.5
1.8
1.7
G
zi
G
G
G
3z
0.8
0.4
2.2
1.7
2.0
2.0
2.1
2.1
3.7
G
G
G
2.7
2.1
2.5
2.6
4.2
4.2
3.7
3.6
3.4
4.a
5.3
5.3
90%
85%
1.2
0.3
G
G
1.2
-0.41 6.3
4.0
G
4.8
88 %
75%
86%
88%
TLC (liters)
FRC (liters)
Normal
Flexed
Normal’
1.2
3.3
2.9
5.7
iiT
1.1
1.1
3.2
3.0
0.3
1.0
0.9
G
1.9
i7
NOTE: FEV, = forced expiratory volume in 1 second; FVC = forced vital capacity: FEF 25_rs = forced expiratory flow between 25 and 75 percent of the FVC; Vso = instantaneous flow rate at 50 percent of the FVC; FEV 1% = FEV,:FVC; TLC = total lung capacity; FRC = functional residual capacity; RV = residual volume. l The head position preferred by the patient. + Measured value Predicted value
Figure 3. Patient 1. Lateral tomograms of larynx and trachea. A, on the left the patient’s head is flexed. The arrows indicate the tracheal air column which is narrowed to a thin slit. B, on the right, the patient’s head is in its normal extended position. The tracheal air column (arrows) is now widely patent. Both tomographic cuts are at the same level. The air-filled esophagus can be seen posteriorly. September 1980
The American Journal of Medicine
Volume 89
489
UPPER AIRWAY OBSTRUCTION IN MORQUIO’S DISEASE-PRITZKER
tracheomalacia and obstructive pulmonary disease who have been shown to have tracheal collapse. Pathologic study of these patients has shown a deficiency in the absolute amount of cartilage, loss of cartilage rigidity and loss of elastic tissue [9]. Although histologic confirmation of abnormal tracheal cartilage was not considered to be warranted in our patients, the findings of tracheal obstruction and tracheal buckling during expiration are consistent with this pathogenesis. Tracheal or reconstructive surgery was considered for Patient 1; however, neck surgery in patients with Morquio’s disease is both technically difficult and
ET AL.
hazardous because of their marked spinal deformities [S]. After considering the surgical risks, the patient declined both tracheal reconstructive surgery and tracheostomy. In patients with Morquio’s disease, who demonstrate both spinal cord compression and tracheal collapse, simultaneous corrective surgery might be considered. ACKNOWLEDGMENT
We thank Dr. Robert J. Rotenberg for referring Patient and Dr. Gregory Grabowski for referring Patients 2 and 3. 1
REFERENCES 1.
2. 3. 4. 5.
470
Hope EOS:Some aspects of respiratory function in three siblings with Morquio-Bra&ford disease. Thorax 1969; 28: 335. Buhain W: Pulmonary function in Morquio’s disease: a study of two siblings. Chest 1977; 68: 41. Fraser RG, Pare ]A: Diagnosis of diseases of the chest, vol III, 2nd ed. Philadelphia: WB Saunders, 1979. McKusick VA: Heritable disorders of connective tissue, 4th ed. St. Louis: CV Mosby, 583: 1972. Kopits S: Orthopedic complications of dwarfism. Clinical
September 1980 The American Journal of Medicine
Orthop 1976: 114: 153. Murray 1: Pulmonary disability in the Hurler syndrome. N Engl J Med 1954; 261: 378. 7. Caffey J: Gargoylism: study of pathologic lesions and clinical review of 12 cases. Am J Dis Child 1948; 76: 239. 8. de Lange C: Some remarks on gargoylism. Acta Paediat Stand 1943-44; 31: 398-416. 9. Campbell A: Tracheobronchial collapse, a variety of obstructive respiratory disease. Br J Dis Chest 1963; 57: 174. 6.
Volume 89