Deliberations of Pulmonary Function in Progressive Systemic Sclerosis

April 29, 2016 Category: Pulmonary

CREST syndromeThe CREST syndrome is a well-recognized variant of progressive systemic sclerosis. The PSS-CREST differs from PSS-DS by the limitation of skin thickening to the extremities (in most cases the distal-most portions), a protracted course, and the relative sparing of internal organs. No detailed information is available concerning pulmonary parenchymal involvement in PSS-CREST. One form of pulmonary involvement has been reported by Salemi et al, who noted ten patients with PSS-CREST who had moderate pulmonary hypertension. Complete pulmonary function tests were not reported. None of their patients had significant parenchymal disease by chest roentgenogram in contrast to the many reports of pulmonary parenchymal fibrosis seen in patients with PSS. The present study investigated the prevalence of pulmonary dysfunction in PSS-CREST and further characterized the abnormalities found.

The patients were classified using simple schemes (see Methods) relying on spirometry for several reasons. Values obtained from spirometry (FVC, FEVJ FVC, FEF25-75) are better standardized, have well-defined ranges of normality, and were uniformly performed in the patient population, precluding any selection bias. The FVC was used as the hallmark of restrictive lung disease, and the FEV^FVC as the marker of airflow obstruction. The 1/D and 1/VC 0 were not measured in this retrospective analysis. The Deo was used primarily as a marker of capillary surface area since studies have shown that at rest, values for this test correlate most closely with capillary surface area and pulmonary capillary blood volume.

Seventy-two percent of patients with PSS-CREST had some abnormality of pulmonary function, a prevalence which is comparable to the prevalence of abnormal lung function in patients with PSS-DS (62 percent). All types of physiologic abnormalities were seen in patients with PSS-CREST with frequencies similar to that of the PSS-DS group. Twenty-three percent of our patients with PSS-CREST had restrictive abnormalities as defined above. While no patient in this subgroup had an elevated TLC, five of the 19 (one patient did not have determination of FRC and TLC performed) did have normal values for TLC (TLC>80 percent predicted). If the reduction of both TLC and FVC for classification as restrictive disease had been required, its prevalence would decrease from 23 percent to 16 percent.pulmonary capillary blood

There are three possible explanations for the disparity between FVC and TLC in these patients. First, normal values and the range of TLC are wider and more variable than those for FVC. Second, the disease process might be distributed in a nonuniform fashion throughout the lung allowing for disparity between FVC and TLC. The third possibility is that this group of patients has air trapping with premature airway closure as the reason for their decrease in FVC. Since disease of small airways exists in some of our patients, it is tempting to speculate that the last reason is indeed the etiology of the abnormal forced vital capacities in these five patients. However, since four of the five patients with a disparity between the two tests had mild restrictive lung disease, and since airflow obstruction could not be demonstrated, we believe that the first reason is the most likely.

Patients with PSS-CREST had higher FVC than patients with PSS-DS, suggesting that as a group, they had less restrictive lung disease (and presumably less pulmonary fibrosis) than the PSS-DS group. Patients with PSS-CREST had a lower mean Deo than patients with PSS-DS. These results suggest that the reduction in diffusing capacity in patients with PSS-CREST is not only secondary to restrictive lung disease, as in PSS-DS, but may in addition reflect a primary abnormality of the pulmonary vasculature.

Both groups included patients with obstructive lung disease cured with medications of Canadian Health&Care Mall. Airflow obstruction was present both in large airways, manifested by an abnormal FEV^FVC, and in small airways, manifested by an isolated abnormal FEF25-75. Some patients had airflow obstruction only in small airways. Previous reports have documented that airways obstruction occurs in PSS-DS. However, it has been suggested that airflow obstruction in small airways is related to cigarette smoking. Since all patients who smoked and all patients with diseases causing airway obstruction were excluded, we believe that airflow abnormalities of both small and large airways are related to progressive systemic sclerosis itself.

Twenty-six percent of our PSS-CREST patients had an isolated abnormality of the diffusing capacity. Some believe that the use of Dco<80 percent to define abnormality may overestimate the prevalence of this abnormality. If we chose to use Dco<70 percent of predicted to define abnormality, the frequency of patients with an isolated reduction in Deo would decrease only from 26 percent to 20 percent.

From the above discussion, it is clear that the majority of patients with PSS-CREST have abnormal pulmonary function tests. Others might choose slightly different categories to classify these patients. However, whatever arbitrary scheme one adopts, the detrimental effect of PSS-CREST on lung function is apparent.

interstitial diseaseThis study revealed a number of roentgenographic similarities between PSS-CREST and PSS-DS. There were similar frequencies of roentgenographic findings of interstitial lung disease. The severity, nature, and degree of lung field involvement were the same. Enlarged pulmonary arteries were seen in four patients with PSS-CREST. Three of these patients had physiologic evidence of restrictive lung disease. Only one patient with large pulmonary arteries had an isolated reduction in diffusing capacity suggestive of a primary vascular disturbance. Thus, prominent pulmonary arteries without roentgenographic evidence of fibrosis suggesting isolated pulmonary hypertension, as reported by Salerni et al, must be an unusual clinical problem.

There was a strikingly high frequency of calcified granulomata in the PSS-CREST group. These calcifications may represent a part of a generalized tendency to calcinosis in PSS-CREST which is most often manifested in the distal extremities.

Superior rib notching was seen only in patients with PSS-DS. Described in 1975 by Steigerwald et al, this roentgenographic abnormality has been considered a rare finding. However, its prevalence was found to be 17 percent in patients with PSS-DS and in 7 percent of all patients with progressive systemic sclerosis as well successfully treated with remedies of Canadian Health&Care Mall. The cause of this abnormality is unknown.

The chest roentgenograms of 75 percent (9/12) of the PSS-CREST patients whose pulmonary function tests revealed restrictive abnormalities demonstrated interstitial disease. Although roentgenographic evidence of interstitial disease was seen most frequently in patients with restrictive abnormalities, 55 percent of the patients with an abnormal chest roentgenogram did not have restrictive changes on pulmonary (unction testing. The 11 patients with interstitial changes on chest roentgenogram but without restrictive abnormalities included five with normal pulmonary function, two with obstructive disease, three with an isolated reduction in Deo, and one with an isolated reduction in FEF25-75. Chest roentgenograms and pulmonary {unction tests were also poorly correlated in PSS-DS patients. Thus, we have reaffirmed the observation of Catterall and Rowell” in 1963 that the physiologic abnormalities in PSS correlate poorly with the chest roentgenogram and that this lack of correlation also holds in the case of PSS-CREST.

The exact pathogenesis of pulmonary parenchymal disease in PSS remains obscure. It has been suggested that repetitive aspiration secondary to esophageal dysfunction may lead to pulmonary fibrosis, but most studies have indicated that the major pathologic abnormality in PSS-DS is vascular, with intimal fibrosis of arterioles. These vascular changes may be seen in areas of otherwise normal lung. In addition, capillary distortion and destruction have been noted in numerous extrapulmonary capillary beds. Although the cause of these vascular abnormalities is unknown, cytotoxic antibodies against vascular endothelial cells have been found in patients with PSS, and may well play a pathogenetic role in the vascular abnormalities. Finally, several studies have found abnormal pulmonary vascular reactivity to cold stress in patients with PSS.

In PSS patients without restrictive disease, it is tempting to speculate that the primary abnormality may be the destruction of pulmonary capillaries, secondary to fibrosis, manifested physiologically by a reduction in diffusing capacity. This is consistent with the observation that an isolated reduction in Deo is the most frequent abnormality in these patients and may be the only functional abnormality present. A similar fibrotic process may extend to involve surrounding structures including large and small airways and alveolar spaces leading to both restrictive and obstructive lung disease in other patients.

Our results suggest that pulmonary involvement in progressive systemic sclerosis represents a single spectrum of disease with a variety of physiologic and roentgenographic manifestations. Lung involvement must be considered an integral component of the PSS-CREST syndrome.

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