Ankylosing spondylitis (AS) is a chronic inflammatory disorder of unknown aetiology, affecting primarily the joints of axial skeleton. It is a systemic disorder with several extra-articular manifestations that include ocular, cardiovascular and neurological complications.(1) Pulmonary involvement is usually recognized in patients with a long history of joint disease, and manifests either as chest wall restriction due to involvement of thoracic cage, or as upper lobe fipobullous disease.(2) Pulmonary parenchymal disease, unless extensive, is typically clinically silent. Radiographic abnormalities are generally seen only in the presence of advanced disease. In view of the systemic and progressive nature of AS, it is likely that onset of pulmonary involvement is much earlier than its clinical or radiological recognition. Pulmonary function tests may help to identify lung involvement. Although restrictive ventilatory defects have been described in these patients, these abnormalities have been largely ascribed to diminished chest wall mobility.(3) It is not possible to differentiate chest wall from pulmonary interstitial involvement using routine studies. Study of static pulmonary mechanics can better characterize the contribution of lung fiposis to these changes.

A few studies have previously documented normal or reduced lung compliance in patients with AS.(3-7) However, most reports included patients with varying stages of established AS, and information on lung mechanics is rather scanty. We performed a detailed analysis of static pulmonary mechanics in patients with AS who had no obvious clinical or radiological evidence of pulmonary disease.

Patients and Methods

The study was conducted on previously diagnosed patients with AS, attending the Rheumatology Clinic of this Institute during a six-month period. Diagnosis in these patients had been established on the basis of modified New York criteria.(8) Patients with respiratory symptoms (dyspnoea and/or cough) or abnormal plain chest radiographs were not included. Current or former smokers, as well as patients with concomitant cardiopulmonary disorders, were also excluded. The nature and purpose of the study were explained to each eligible subject and informed consent was obtained prior to pulmonary function testing. The study protocol had been approved by our Hospital Ethics Committee.

Spirometry was performed on a dry rolling seal spirometer (Spiroflow, P K Morgan Ltd., UK). Vital capacity (VC), forced expiratory volume in first second (FEV(1)) and peak expiratory flow were measured and compared to norms for healthy north Indian adults previously derived by us.(9) Static expiratory pressure-volume relationship was generated using a computerized whole body plethysmograph system (Autolink; P K Morgan Ltd., UK). Oesophageal pressure was measured through a thin latex balloon positioned in the oesophagus at approximately 40 cm from the nares and inflated with 0.4 ml air.(10) After a period of tidal peathing, during which the position of functional residual capacity (FRC) was identified, each subject took a series of three full inspirations to total lung capacity (TLC) to ensure a constant volume history. Static transpulmonary pressure at TLC (P(TLC)) was recorded at the end of third inspiration as the difference between mouth and oesophageal pressures. Patients were subsequently asked to exhale slowly in a stepwise fashion while the airway was intermittently occluded by a shutter placed close to the mouthpiece. During each occlusion, patients kept their glottis open to measure static transpulmonary pressure and lung volume. This procedure was repeated until 10 or more readings were obtained. Static lung compliance (C(st)) was computed as the slope of the composite pressure-volume curve thus plotted in its relatively straight portion above the FRC. The observed TLC was compared to previously described norms for healthy north Indian adults.(11,12) Pressure-volume data were also subjected to monoexponential analysis, using the equation V = V(max) - Ae(-KP)where V is the lung volume, V(max) is the extrapolated lung volume at infinite distending pressure, K is a constant describing the shape of the curve, P is the static transpulmonary pressure and A = V(max) - V(0) (where V(0) is the volume extrapolated to zero transpulmonary pressure).(13,14) The observed values for compliance, shape constant (K), and P(TLC) were compared to predicted norms previously described for healthy subjects.(15) Limits of normality for all pulmonary function variables were defined as the predicted value ± 1.645 times the residual standard deviation of the relevant regression equation.(16)

Results

Seventeen patients (16 men and one woman) with mean age of 28.2 ± 11.9 years (range 16-63 years) were studied. They were symptomatic with low backache of one to 20 years’ duration. Seven patients had peripheral arthritis involving knee and/or hip joints, and another had an episode of uveitis six months prior to pulmonary function evaluation (Table 1).

Vital capacity was reduced in five (29.4%) patients (Table 2). A restrictive ventilatory defect, defined as a diminished TLC, was present in six (35.3%) patients; TLC ranged from 85-105% of predicted in the remaining patients. No patient had any obstructed defect, as seen by normal FEV1/VC values in all subjects (Table 2). P(TLC) was reduced in one (5.9%) and increased in seven (41.2%) patients. C(st) was reduced in nine (52.9%) patients; only five of them had reduced TLC (Table 2). In another patient, C(st) was increased but TLC was within normal limits. All patients with normal C(st), except one, had normal lung volumes. Detailed analysis of pressure-volume data showed that K was reduced in all except one patient with low C(st). This pattern suggested reduced lung distensibility.

Abnormalities in static lung mechanics were detected both in patients with and without peripheral arthritis and/or extra-articular manifestations (Table 2). There was also no correlation between the duration of articular symptoms and impairment of pulmonary mechanics. Overall, three poad types of abnormalities were identified (Fig 1): (a) four (23.5%) patients had normal TLC, yet C(st) and K were found reduced; (b) five (29.4%) patients had a restrictive ventilatory defect (reduced TLC) as well as reduced C(st) , and four of them had a low K; (c) one (5.9%) patient had normal TLC but elevated C(st) and K.

Discussion

We have studied patients of AS with no obvious clinical or radiological evidence of pulmonary complications of the disease. To assess the true contribution of the underlying disease, we had excluded all current and former smokers, as well as patients with concomitant cardiopulmonary disorders. A restrictive ventilatory defect in patients with AS has traditionally been attributed to limited chest wall expansion.(3) The methodology used in measuring lung compliance in this study eliminates the contribution from thoracic cage abnormalities, as our pressure measurements were the difference between alveolar pressure (represented by mouth pressure under static conditions) and pleural pressure (represented by oesophageal pressure). Hence the abnormalities detected, in all probability, reflected pulmonary complications of AS in these patients. It has earlier been suggested that of all respiratory function parameters, those derived from a static pressure-volume curve are the best predictors of the degree of pulmonary fiposis.(17)

Compliance was reduced in nine of 17 subjects included in this study. Comparison of our results with those obtained by previous investigators is, however, difficult because of several reasons. Earlier studies, for example, had not employed limits of normality as is now recommended for interpretation of pulmonary function tests.(16) Thus values below the predicted normal were reported as reduced or normal using arbitrary cut-off points, which had often not been clearly defined. Secondly, different techniques had been used to measure C(st) in various studies. Finally, the composition of our study population was different from several previous reports. For example, 60% patients with low or borderline compliance in one study had associated pulmonary disorders that could have partly explained this abnormality.(5) In another study, four of 11 patients found to have compliance values below the predicted normal had complicating pulmonary diseases.(3) However, in a study on patients with no pulmonary symptoms and normal chest radiographs, lung compliance values were no different from those in the reference study population.(6) In another study carried out on 21 patients with no clinical evidence of lung disease, there was close agreement between observed and predicted values in all but three patients.(4) Further analysis was, however, not provided in either study.

Alterations in lung parenchyma start much earlier than when radiologically recognised. In fact, cases have been documented where pulmonary manifestations have appeared quite early in the course of disease or have even antedated joint symptoms.(18,19) It also appears that interstitial changes could be diffuse and not merely confined to the upper lobes.20 Whether these changes are related to an ongoing inflammatory process is not clear. The observation that decreased lung volumes were related to inflammatory intensity of disease may suggest an inflammatory involvement of the lung parenchyma.(6) Although characteristic features suggestive of alveolitis have not been identified on analysis of ponchoalveolar lavage fluid in these patients, a non-specific inflammatory response has been seen.(21,22) This early pulmonary involvement can explain loss of compliance seen in half of our patients.

The static lung pressure volume relationship is non-linear over a substantial portion of lung volumes. C(st), which represents the slope of this curve in its relatively linear portion, is only a gross approximation of static pulmonary mechanics. Exponential analysis of pressure-volume data better describes static lung mechanics over a wide range of lung volumes.(13,14) The shape constant of this curve (K), the single most important variable describing this curve, is an index of lung compliance. Unlike compliance, it is largely independent of sex, ethnicity, patient effort and lung size.(14,23) Among patients with restrictive ventilatory defects, exponential analysis also helps to differentiate restriction due to reduced elastic properties (low value for K) from that due to loss of lung volume (normal K).(24) C(st) was reduced in nine of 17 of our patients. Interstitial fiposis can induce restriction either by reducing distensibility or by obliterating existing alveoli. Detailed analysis of pressure volume data helped in identifying reduced distensibility as the dominant pathophysiology in these patients. The severe reduction in compliance and K values seen in some patients suggests that lung involvement is diffuse rather than focal; similar findings have earlier been described on HRCT scans carried out in patients with AS.(19)

One of our patients had increased C(st) and an increased value for K. This combination is seen in conditions characterized by distension of airspaces, such as emphysema.(23) This patient, however, had a normal TLC. The precise reason for such abnormality in a non-smoking patient is not clear. Although bullous lesions are described in patients with long standing disease, this patient had been symptomatic for only three years. Recently, panacinar and paraseptal emphysematous changes have been described on HRCT in these patients.(20) Whether this patient had similar changes is a matter of conjecture.

Only one patient in our study had reduced P(TLC). Majority of patients had normal values and 6 (35.3%) showed high P(TLC). Previous studies had shown a reduction in mean P(TLC) values in patients with AS.(3,6,7) The reason for such a change is not clear. It is known that although rib mobility decreases in patients with AS, a supranormal diaphragmatic excursion helps to maintain normal ventilation.(26,27) The normal or increased diaphragmatic strength may, however, be overwhelmed by a reduced strength or atrophy of intercostal or accessory muscles, or both.(28) It has been speculated that immobilization of these muscles due to thoracic rigidity and decreased inspiratory muscle activation are important factors, especially in long standing cases. Since most of our patients were evaluated relatively early in the course of disease, it is possible that the strength of inspiratory muscles was well preserved and the increase in P(TLC) was a reflection of increased diaphragmatic excursion.

In conclusion, the evaluation of static lung mechanics can identify pulmonary interstitial fiposis early in the course of disease in several patients with AS, even when they do not have significant clinical and radiological findings. This suggests that pulmonary involvement in these patients possibly begins much earlier than what has been generally presumed, and is probably diffuse rather than confined to the apical portions of the lung.

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