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Circulating antibodies to lung protein(s) in patients with cryptogenic fibrosing alveolitis.

BACKGROUND: It has been hypothesised that cryptogenic fibrosing alveolitis has an immunological pathogenesis mediated by T lymphocytes. It is, however, recognised that patients may show dysregulation of the humoral immune system and that the presence of large numbers of B lymphocytes in open lung biopsies may be associated with a poor prognosis. Evidence of a role for the humoral immune system in the pathogenesis of cryptogenic fibrosing alveolitis has been suggested, but attempts to demonstrate circulating immunoglobulin to antigen within the lung have been inconclusive. METHODS: Plasma samples from 22 patients with cryptogenic fibrosing alveolitis, 22 patients with sarcoidosis, and 17 healthy controls were screened by SDS-PAGE and Western blotting for the presence of autoantibodies to lung proteins derived from cryptogenic fibrosing alveolitis, sarcoid and control lung tissue, as well as four normal non-pulmonary tissues. Possible site(s) of target protein(s) within the lung tissue were identified by immunohistochemical examination using IgG purified from the plasma of six patients and two controls. RESULTS: Eighteen of the plasma samples from patients with cryptogenic fibrosing alveolitis had reactive IgG to lung protein(s) in the 70-90 kDa molecular weight range compared with five of 18 plasma samples from patients with sarcoidosis and one of 17 controls. Plasma from patients with cryptogenic fibrosing alveolitis recognised antigen(s) of the same molecular weight in control and sarcoid lung tissue, but not non-pulmonary tissues, with a similar frequency. Immunohistochemical staining of cryptogenic fibrosing alveolitis biopsy material using IgG purified from plasma samples from patients with cryptogenic fibrosing alveolitis, but not control samples, revealed fine linear positivity in the lung parenchyma in a pattern suggestive of reaction with alveolar lining cells. The pattern was cytoplasmic/membranous and not nuclear. CONCLUSIONS: Patients with cryptogenic fibrosing alveolitis have a high frequency of plasma IgG autoantibodies to protein(s) within lung tissue associated with alveolar lining cells. This is believed to be the site where immunological injury occurs in cryptogenic fibrosing alveolitis, but the significance of these antibodies to the aetiology and pathogenesis is as yet unclear.

Aged↗

The dangers of intraosseous fibrosing agent injection in the treatment of bone cysts. The origin of major complications shown in a rabbit model.

Direct intraosseous injection of fibrosing agent is widely used in the treatment of aneurysmal bone cysts. The purpose of this study was to evaluate the consequences of fibrosing agent penetrating the medulla of bones. This may be the case when, by mistake, the fibrosing agent is administered into the medulla or when the wall of the cyst ruptures and fibrosing agent is able to drift into the medulla. Twelve rabbits were injected transcutaneously with a fibrosing agent directly into the proximal metaphysis of the tibia. Prior to injection 0.5 ml of liquid-like, bloody, intraosseal tissue was aspirated, then 0.5 ml of fibrosing agent was administered. Fibrosing agent was introduced slowly (20 s) to avoid overpressure. Nine rabbits (75%) died within minutes after the introduction of fibrosing agent. A full body roentgenogram was taken of each rabbit and the animals that died underwent autopsy to find the exact cause of death. Roentgenograms of the chest showed massive multiple pulmonary emboli confirmed in all lethal cases by the autopsy. This animal model was created to draw attention to the dangers of any leakage of the fibrosing agent into the medulla of bones.

Animals↗

DSM-III diagnoses of patients with myofascial pain syndrome (fibrositis).

Rheumatology centers report that chronic pain patients with myofascial pain (fibrositis) are prone to psychiatric pathology. However, the distribution of DSM-III diagnoses in this population is unknown. This distribution is reported for 238 chronic pain patients with fibrositis. Statistical comparisons of men and women were also made with regard to the prevalence of each diagnosis, and the results were compared to published DSM-III diagnoses prevalence data for mixed chronic pain patients and rheumatology fibrositis patients. In our sample, women with fibrositis were equally as likely as men with fibrositis to have current depression. Within the general chronic pain population, women are more likely to have current depression. The incidence of current major depression and current and past major depression was much lower in our fibrositis sample than that reported by rheumatology programs. These results indicate that there may be psychiatric differences between chronic pain patients with and without fibrositis. Fibrositis patients in rheumatology programs may also be psychiatrically different from chronic pain program patients with fibrositis.

Adult↗

High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis.

BACKGROUND: Fibrosing colonopathy has been reported in young children with cystic fibrosis, the majority of whom take high-strength pancreatic-enzyme supplements to control intestinal malabsorption. We conducted a case-control study in the United States to investigate the relation between dose and type of pancreatic-enzyme supplement and fibrosing colonopathy. METHODS: Children with histopathologically confirmed cases of fibrosing colonopathy who required colectomy for colonic strictures from January 1, 1990, through December 31, 1994, were identified. Each of these patients was matched according to age at the time of surgery and medical center with up to four controls with cystic fibrosis who did not have fibrosing colonopathy. RESULTS: We studied 29 patients (mean age, 5.0 years) with fibrosing colonopathy (case patients) and 105 controls (mean age, 5.2 years). The mean dose of pancreatic-enzyme supplement was 50,046 units of lipase per kilogram of body weight per day for the case patients and 18,985 units per kilogram per day for the controls. A history of gastrointestinal complications attributed to cystic fibrosis and the use of histamine H2-receptor blockers, corticosteroids, or recombinant human DNase (dornase alfa) were associated with a higher incidence of fibrosing colonopathy. After adjustment for a history of such complications and the use of these medicines, the relative risk of fibrosing colonopathy that was associated with a dose of 24,001 to 50,000 units of lipase per kilogram per day, as compared with a dose of 0 to 24,000 units per kilogram per day, was 10.9 (95 percent confidence interval, 1.6 to 71.8), and that associated with a dose of more than 50,000 units per kilogram per day was 199.5 (95 percent confidence interval, 9.9 to 4026.0). The strength, coating, and manufacturer of the products used were not associated with the risk of fibrosing colonopathy. CONCLUSIONS: In young children with cystic fibrosis, we found a strong relation between high daily doses of pancreatic-enzyme supplements and the development of fibrosing colonopathy. Our findings support recommendations that the daily dose of pancreatic enzymes for most patients should remain below 10,000 units of lipase per kilogram.

Case-Control Studies↗

Idiopathic nonspecific interstitial pneumonia: prognostic significance of cellular and fibrosing patterns: survival comparison with usual interstitial pneumonia and desquamative interstitial pneumonia.

Nonspecific interstitial pneumonia (NSIP) has been proposed as a histologic subtype of idiopathic interstitial pneumonia with lung biopsy findings that are inconsistent with those of other idiopathic interstitial pneumonias. NSIP has a broad spectrum of histologic findings and a variable prognosis. The aim of this study was to determine whether it would be preferable to subdivide NSIP into cellular and fibrosing patterns. The authors classified lung biopsies from 101 patients with idiopathic interstitial lung disease as having histologic patterns of desquamative interstitial pneumonia (DIP), usual interstitial pneumonia (UIP), or cellular or fibrosing NSIP. Survival analysis was performed using the Kaplan-Meier method. Due to histologic, clinical, and survival similarities, the patients with idiopathic NSIP with lung biopsies that showed fibrosing as well as fibrosing and cellular patterns were combined into a single group of NSIP, fibrosing pattern. Of the 101 patients, 16 patients (9 women, 7 men) had idiopathic DIP; 56 patients (17 women, 39 men) had idiopathic UIP; 22 patients (7 women, 15 men) had idiopathic NSIP, fibrosing pattern; and 7 patients (2 women, 5 men) had idiopathic NSIP, cellular pattern. The patients had a mean age of 42, 51, 50, and 39 years respectively. Patients with idiopathic NSIP, cellular pattern had a better 5- and 10-year survival than those with idiopathic NSIP, fibrosing pattern (100% vs 90% and 100% vs 35% respectively, p = 0.027). Survival of patients with idiopathic UIP was worse than that of patients with idiopathic NSIP, fibrosing pattern (p = 0.014). The difference, however, was more evident at 5 years (43% vs 90%) than at 10 years (15% vs 35%). The 5- and 10-year survival of patients with idiopathic NSIP, cellular pattern and DIP was 100%, which was significantly better than that of patients with idiopathic UIP (p <0.0001). Based on these data, NSIP should be separated into cellular and fibrosing patterns, because these histologic patterns are associated with different clinical characteristics and prognoses.

Adult↗

Rising mortality from cryptogenic fibrosing alveolitis.

OBJECTIVE: To determine the pattern of mortality ascribed to cryptogenic fibrosing alveolitis and to identify factors that might be important in the aetiology of the disease; and to assess the validity of death certification of the disease. DESIGN: A retrospective examination of mortality ascribed to cryptogenic fibrosing alveolitis in England and Wales between 1979 and 1988 with analysis, by multiple logistic regression, of independent effects of age, sex, region of residence, and social class as indicated by occupation on data for 1979-87; also a retrospective review of hospital records of patients certified as having died of cryptogenic fibrosing alveolitis in Nottingham and of the certified cause of death of patients known to have had the disease. MAIN OUTCOME MEASURES: Time trends in mortality nationally; effects on mortality of age, sex, and region of residence; validity of death certification in Nottingham. RESULTS: The annual number of deaths ascribed to cryptogenic fibrosing alveolitis doubled from 336 in 1979 to 702 in 1988, the increase occurring mainly at ages over 65. Mortality standardised for age for both sexes likewise increased steadily over the period. Deaths due to cryptogenic fibrosing alveolitis were commoner in men (odds ratio 2.24, 95% confidence interval 2.11 to 2.33) and increased substantially with age, being 7.84 (7.24 to 8.49) times higher in subjects aged much greater than 75 than those aged 45-64. Odds ratios of death due to cryptogenic fibrosing alveolitis adjusted for age and sex were increased in the traditionally industrialised central areas of England and Wales (p less than 0.02, maximum odds ratio between regions 1.25), but no significant increase in odds of death was found for manual occupations. Of 23 people whose deaths were registered in Nottingham as having been due to cryptogenic fibrosing alveolitis, 19 were ascertained from clinical records to have had the disease. Only 17 of 45 patients known to have had cryptogenic fibrosing alveolitis in life were recorded as having died from the disease. CONCLUSIONS: The diagnostic accuracy of death certification of cryptogenic fibrosing alveolitis is high, but the number of deaths recorded as being due to the disease may underestimate the number of patients dying with the disease by up to half. Mortality due to the disease is increasing, and the male predominance and regional differences in mortality suggest that environmental factors are important in its aetiology.

Adolescent↗

High resolution computed tomographic assessment of asbestosis and cryptogenic fibrosing alveolitis: a comparative study.

BACKGROUND: The aim of this study was to compare the distribution and configuration of lung opacities in patients with cryptogenic fibrosing alveolitis and asbestosis by high resolution computed tomography. METHODS: Eighteen patients with cryptogenic fibrosing alveolitis and 24 with asbestosis were studied. Two independent observers assessed the type and distributions of opacities in the upper, middle, and lower zones of the computed tomogram. RESULTS: Upper zone fibrosis occurred in 10 of the 18 patients with cryptogenic fibrosing alveolitis and in six of the 24 patients with asbestosis. A specific pattern in which fibrosis was distributed posteriorly in the lower zones, laterally in the middle zones, and anteriorly in the upper zones was seen in 11 patients with cryptogenic fibrosing alveolitis and in four with asbestosis. Band like intrapulmonary opacities, often merging with the pleura, were seen in 19 patients with asbestosis but in only two with cryptogenic fibrosing alveolitis. Areas with a reticular pattern and a confluent or ground glass pattern were the commonest features of cryptogenic fibrosing alveolitis (15 and 14 patients respectively) but were uncommon in asbestosis (four and three patients). Pleural thickening or plaques were seen in 21 patients with asbestosis and in none with cryptogenic fibrosing alveolitis. CONCLUSION: Apart from showing pleural disease high resolution computed tomography showed that confluent (ground glass) opacities are common in cryptogenic fibrosing alveolitis and rare in asbestosis whereas thick, band like opacities are common in asbestosis and rare in cryptogenic fibrosing alveolitis.

Adult↗

Accuracy of the typical computed tomographic appearances of fibrosing alveolitis.

BACKGROUND: Open lung biopsy is often performed to confirm the diagnosis in patients with suspected fibrosing alveolitis. The superior sensitivity and specificity of high resolution computed tomography (CT) over chest radiography in various diffuse lung diseases suggest that the characteristic appearance of fibrosing alveolitis on high resolution CT might render biopsy confirmation unnecessary. METHODS: The chest radiographs and high resolution CT scans of 86 patients (41 with fibrosing alveolitis and 45 with various other diffuse lung diseases) were examined individually and independently by two observers. No clinical information was given and the observers gave a level of confidence when the diagnosis was thought to be fibrosing alveolitis. RESULTS: The observers correctly and confidently discriminated between fibrosing alveolitis and other diffuse lung diseases on high resolution CT with an accuracy of 88% and on chest radiography with an accuracy of 76%. The false negative rate for fibrosing alveolitis diminished from 29% on chest radiography to 11% on high resolution CT. The false positive rate on chest radiography was 19% and on high resolution CT 13%; the false positive diagnoses on CT were the result of a few conditions (extrinsic allergic alveolitis, sarcoidosis, cryptogenic organising pneumonia, and pulmonary eosinophilia) which mimicked some of the CT features of fibrosing alveolitis. The superficial similarity of the CT patterns of these conditions are discussed. CONCLUSIONS: High resolution CT is superior to chest radiography in establishing the diagnosis of fibrosing alveolitis and the typical CT appearances are virtually pathognomonic. The diagnostic advantages of CT over chest radiography should further reduce the need for open lung biopsy in this condition.

Biopsy↗

Exposure to commonly prescribed drugs and the etiology of cryptogenic fibrosing alveolitis: a case-control study.

Cryptogenic fibrosing alveolitis is an interstitial lung disease of unknown etiology. Since pulmonary fibrosis is a recognized, if rare, complication of certain drug exposures, including antidepressants, betablockers, antibiotics, anticonvulsants, and nonsteroidal antiinflammatory drugs (NSAIDs), we tested the hypothesis that exposure to these drugs might contribute to the etiology of cryptogenic fibrosing alveolitis. Lifetime drug exposure data were collected from general practitioner records for 141 cases of cryptogenic fibrosing alveolitis and 246 age-, sex-, and community-matched control subjects from the Trent region of England. Additional data on lifetime smoking habits were obtained by postal questionnaire. The odds of disease in relation to ever exposure to antidepressants, betablockers, antibiotics, anticonvulsants, and NSAIDs were calculated by conditional logistic regression. For drug groups significantly associated with cryptogenic fibrosing alveolitis, subset analyses were performed to investigate the effects of individual drugs. Cryptogenic fibrosing alveolitis was associated with exposure to antidepressants (odds ratio [OR] 1.79 [95% CI 1.09-2.95], p = 0.022) and specifically to imipramine (OR 4.79 [1.50-15.3], p = 0.01), dothiepin (OR 2.37 [0.99-5.69], p = 0.05), and mianserin (OR 3.27 [1.11-9.61], p = 0.03). The magnitude of the overall effect of antidepressants was not changed by excluding all drug exposures within the 5 yr preceding the diagnosis of cryptogenic fibrosing alveolitis (OR 1.62 [0.94-2.77], p = 0.081), nor were the strong individual effects of imipramine (OR 5.72 [1.54-21.2], p = 0.009) and dothiepin (OR 5.58 [1.12-27.8], p = 0.036). These estimates were not appreciably affected by controlling for smoking history. The attributable risk for antidepressant exposure was in the region of 9-14%. No significant association was noted between cryptogenic fibrosing alveolitis and the four other drug groups in the primary hypothesis. The results of this study suggest that some antidepressant drugs can cause cryptogenic fibrosing alveolitis.

Adrenergic beta-Antagonists↗

Hypothesis: exposure to solvents may cause fibrosing alveolitis.

The incidence of fibrosing alveolitis, which can be caused by many agents, is increasing. In a proportion of patients, the aetiology is unknown (cryptogenic fibrosing alveolitis), but it has been suggested that environmental factors may play an important, but unrecognized, role in its pathogenesis. A review of the literature suggests that there may be a link between exposure to solvents, widespread occupational pollutants, and fibrosing alveolitis. Experimental work in animals has shown that exposure to solvents produces changes in the lung similar to those found in fibrosing alveolitis. Occupational exposure to a wide number of solvents has been associated with the development of systemic sclerosis. Pulmonary involvement in systemic sclerosis is morphologically indistinguishable from fibrosing alveolitis, and a close relationship between the two diseases seems to exist. This close relationship and the experimental work linking solvent exposure to fibrosing alveolitis suggest that solvent exposure may be one cause of cryptogenic fibrosing alveolitis. Determination of any occupational exposure of patients with cryptogenic fibrosing alveolitis may help in the understanding and prevention of this disease.

Acute Disease↗

Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis.

BACKGROUND: Cryptogenic fibrosing alveolitis (synonymous with idiopathic pulmonary fibrosis) is a clinically heterogeneous condition in which the precipitating factor is unclear. Both environmental and infective factors have been implicated. An association between Epstein-Barr virus (EBV) and cryptogenic fibrosing alveolitis was suggested over a decade ago by a study based on EBV serology, but the significance of this has been unclear. METHODS: Lung tissue obtained surgically from patients (n = 20) with cryptogenic fibrosing alveolitis was investigated for evidence of EBV replication and compared with lung tissue from 21 control patients. Fourteen of the 20 patients had received no specific therapy for cryptogenic fibrosing alveolitis at the time of biopsy. Monoclonal antibodies directed against the EBV viral antigens, EBV viral capsid antigen (VCA) and gp 340/220 antigen, which are expressed during the lytic phase of the EBV life cycle, were studied. RESULTS: Fourteen (70%) of the 20 patients with cryptogenic fibrosing alveolitis were positive for both EBV VCA and gp 340/220 compared with two (9%) of the 21 controls. In the patients with cryptogenic fibrosing alveolitis viral replication was localised to pulmonary epithelial cells using epithelial cell markers, and immunohistochemical analysis confirmed the staining to be within type II alveolar cells. CONCLUSIONS: This is the first report of in vivo EBV replication within epithelial cells of the lower respiratory tract in an immunocompetent human host. Furthermore, this suggests that EBV may be an immune trigger or contribute to lung injury in cryptogenic fibrosing alveolitis, thus offering a potential new avenue of treatment.

Adult↗

Type III and type I procollagen markers in fibrosing alveolitis.

Deposition of types I and III collagen is a typical feature in the development of pulmonary fibrosis. We assessed the propeptides of these procollagens as prognostic markers in 18 patients with fibrosing alveolitis. We analyzed the amino-terminal propeptide of type III procollagen (PIIINP) and the carboxy-terminal propeptide of type I procollagen (PICP) from samples of bronchoalveolar lavage fluid (BALF) and serum, and also estimated their concentrations in epithelial lining fluid (ELF) by the urea method. The level of PIIINP in serum (p < 0.05), BALF (p < 0.05), and ELF (p < 0.05), and the levels of PICP in BALF (p < 0.001) and ELF (p < 0.001) but not in serum, were significantly increased in the patients with fibrosing alveolitis as compared with 17 controls who had been investigated for minor respiratory symptoms. In the BALF and ELF of patients with fibrosing alveolitis, PICP but not PIIINP had significant negative correlations with the specific diffusion coefficient for carbon monoxide (DLCO/ VA). The amino-terminal propeptide of type III procollagen and the carboxy-terminal propeptide of type I procollagen in BALF correlated significantly with one another. During the follow-up period of 6 yr, seven of the 18 patients with fibrosing alveolitis died of the disease, 3 others died of malignancy, and one patient died from an unknown cause. DLCO (p < 0.05) differed significantly between the surviving patients and those who died of fibrosing alveolitis, and detectable PIIINP in BALF predicted death from fibrosing alveolitis (p = 0.05). In conclusion, these results show that PIIINP in BALF, ELF, and serum, and PICP in BALF and ELF, are increased in patients with fibrosing alveolitis. A high level of PICP in BALF, and especially in ELF, suggests a chronic process and increased synthesis of type I collagen in the lungs, whereas PIIINP in BALF and ELF suggests active disease and a poor prognosis.

Biomarkers↗

Severe bilateral fibrosing pleuritis associated with chronic chylothorax in five cats and two dogs.

Severe bilateral fibrosing pleuritis was diagnosed in 5 cats and 2 dogs with chronic chylothorax. All animals were dyspneic on initial examination and remained moderately to severely dyspneic after thoracentesis. Radiographic evidence of fibrosing pleuritis included rounded lung lobes and failure of the lungs to reexpand following effective pleural drainage. Fibrosing pleuritis was also suggested in several animals with radiographic evidence of pleural fluid, in which pleural fluid could not be retrieved. Macroscopically, the lung lobes of all animals were compressed and atelectatic to various degrees, and the pleura appeared to be diffusely thickened and roughened. In several animals, fibrous adhesions were found between the parietal and visceral pleura of some lobes. Lung lobes were markedly constricted and appeared as small, smooth, rounded hilar masses in 4 animals. Mild to moderate pulmonary edema was evident in 3 animals at necropsy. Six of the 7 animals died (2) or were euthanatized (4) within 72 hours after the diagnosis of fibrosing pleuritis. The fibrosing pleuritis developed in 1 animal with lymphoblastic lymphosarcoma and chylothorax after treatment via passive pleuroperitoneal drainage; this animal was euthanatized because of underlying neoplasia. One cat, in which decortication was performed and resulted in marked reexpansion of the lung lobes, died 4 hours after surgery with signs compatible with pulmonary edema. On the basis of our findings, we suggest that animals with chronic chylothorax are at risk to develop fibrosing pleuritis. Furthermore, animals with severe bilateral fibrosing pleuritis should be given extremely guarded prognoses.

Animals↗

Comparative and experimental pathology of fibrosing colonopathy.

Although the occurrence of fibrosing colonopathy is temporally associated with the introduction of high-strength pancreatic enzyme supplements, its pathogenesis remains uncertain. The UK case-control study showed fibrosing colonopathy to be associated with high doses of high-strength pancreatic enzyme supplements and with a group of brands which occupy only 30% of the market. Two alternative hypotheses were proposed to explain the aetiology of fibrosing colonopathy: exposure to high levels of enzymes or to as yet unidentified components of the formulation. Comparison of the anatomical pathology of fibrosing colonopathy with that of previously encountered forms of obstructive gastrointestinal pathology, such as stricturing lesions due to potassium chloride preparations and nonsteroidal anti-inflammatory drugs, confirmed it to be a previously unencountered, long-segment lesion of the colon. Thus the use of the descriptive term 'stricture' is a misnomer leading to much clinical confusion when discussing obstructive bowel pathology in cystic fibrosis patients. Gavage studies in the rat with one of the two monomers (ethyl acrylate) forming the methacrylic acid copolymer (Eudragit L30D55) used for the enteric coating of the high-strength pancreatic enzyme supplements, have shown pathology comparable to fibrosing colonopathy. These findings prompted a series of exploratory studies in adolescent pigs. After seven days caecal gavage of Eudragit L30D55 at doses of 10, 50 or 500 mg/kg/day (comparable to human intake), extensive fibrosing colonopathy-like changes, inclusive of dense submucosal fibrosis, were noted at all dose levels in seven out of nine animals. Similar studies of the monomer components of the Eudragit L30D55 copolymer, at dose levels of 0.015 to 50 mg/kg/day, representing possible residues in Eudragit L30D55, did not produce comparable changes. The conclusion is that, although the precise mechanisms have not been elucidated, the role of enteric coatings containing Eudragit L30D55 in the pathogenesis of fibrosing colonopathy requires urgent further study.

Acrylic Resins↗

Aerobic fitness in patients with fibrositis. A controlled study of respiratory gas exchange and 133xenon clearance from exercising muscle.

Aerobic fitness was evaluated in 25 women with fibrositis, by having them exercise to volitional exhaustion on an electronically braked cycle ergometer. Compared with published standards, greater than 80% of the fibrositis patients were not physically fit, as assessed by maximal oxygen uptake. Compared with matched sedentary controls, fibrositis patients accurately perceived their level of exertion in relation to oxygen consumption and attained a similar level of lactic acidosis, as assessed by their respiratory quotient and ventilatory threshold. Exercising muscle blood flow was estimated by 133xenon clearance in a subgroup of 16 fibrositis patients and compared with that in 16 matched sedentary controls; the fibrositis patients exhibited reduced 133xenon clearance. These results indicate a need to include aerobic fitness as a matched variable in future controlled studies of fibrositis and suggest that the "detraining phenomenon" may be of relevance to the etiopathogenesis of the disease.

Adult↗

Clinical characteristics of fibrositis. I. A "blinded," controlled study of symptoms and tender points.

Twenty-two patients with fibrositis, selected from a general medical outpatient population by a screening questionnaire and subsequent evaluation, were compared with age-, sex-, and clinic-matched patients without fibrositis. Although there was a high prevalence of musculoskeletal complaints in both groups, the fibrositis patients had a uniform constellation of symptoms, including axial pain, severe aching and stiffness, morning fatigue, and modulation by specific factors. They also had a higher incidence of tension headache and irritable bowel syndrome. The use of a dolorimeter demonstrated that fibrositis patients had many more areas of localized tenderness than control patients, but also that fibrositis patients did not have diffusely diminished pain threshold and tolerance. Using the criteria of this study, fibrositis appears to be a common and readily definable syndrome within the spectrum of soft tissue rheumatism.

Adolescent↗

Up-regulation of IL-8 secretion by alveolar macrophages from patients with fibrosing alveolitis: a subpopulation analysis.

Neutrophil accumulation in the lower respiratory tract of patients with fibrosing alveolitis is thought to be facilitated by IL-8, a neutrophil chemoattractant primarily secreted by mononuclear phagocytes. The aims of this study were: (i) to explore IL-8 secretion by lung and blood mononuclear phagocytes in subjects with cryptogenic fibrosing alveolitis, systemic sclerosis with and without fibrosing alveolitis, sarcoidosis and normal individuals; (ii) to examine IL-8 secretory heterogeneity in alveolar macrophages and peripheral blood monocytes; and (iii) to correlate alveolar macrophage phenotypic profile to IL-8 secretion. We observed that more monocytes secreted IL-8 than autologous macrophages and that there was heterogeneity in the in vitro IL-8 secretion by alveolar macrophages and peripheral blood monocytes. IL-8 secretion by alveolar macrophages was significantly higher in subjects with fibrosing alveolitis compared with subjects without fibrosing alveolitis, due to a higher percentage of IL-8-secreting alveolar macrophages in the fibrotic group both in the absence (P < 0.002) and presence of lipopolysaccharide (LPS) (P < 0.04) and correlated with bronchoalveolar lavage neutrophil percentage. Using the MoAbs RFD1, RFD7 and RFD9, that distinguish subsets of alveolar macrophages, we have been able to identify associations between secretion of IL-8 and smaller cells and the cells identified by the MoAb RFD7. In situ hybridization of the bronchoalveolar lavage cell population revealed that alveolar macrophages are the predominant source of IL-8 in the lung. We conclude that there is an increased number of IL-8-secreting alveolar macrophages in the lungs of patients with fibrosing alveolitis, and IL-8 secretion by these cells is associated with specific phenotypic profile expression.

Adult↗

Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy.

BACKGROUND: In 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose. METHODS: We retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose. RESULTS: In the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores. CONCLUSIONS: Our data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.

Adolescent↗