Long-term treatment with human immunoglobulin for antisynthetase syndrome-associated interstitial lung disease.

BACKGROUND: Interstitial lung disease-associated antisynthetase syndrome (AS-ILD) carries significant morbidity and mortality. Corticosteroids and immunosuppressive drugs are the mainstay of treatment. Human immunoglobulin (IVIg), an immunomodulator without immunosuppressive properties, is effective in myositis but the evidence supporting its use in ILD is scarce. OBJECTIVE: To describe clinical outcomes of AS-ILD patients receiving IVIg. METHODS: Retrospective analysis of AS-ILD patients. Linear mixed models using restricted maximum likelihood estimation was used to estimate the change in lung function and corticosteroid dose over time. RESULTS: Data from 17 patients was analyzed. Median follow-up was 24.6 months. Fourteen patients had refractory disease. The mean percent-predicted forced vital capacity (FVC%) (p = 0.048) and percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (p = 0.0223) increased over time, while the mean prednisone dose (p < 0.001) decreased over time. Seven patients achieved a >10% increase in FVC%, including two who used IVIg as initial treatment. Five patients showed a >10% increase in DLCO% and TLC%. Nine (53%) patients experienced side effects. CONCLUSIONS: IVIg may be a useful complementary therapy in active progressive AS-ILD but is associated with potential side effects. Fssssurther investigation is required to determine the value of IVIg as an initial treatment in AS-ILD.

Efficacy of TCM therapy of tonifying lung-kidney's Qi-deficiency in a case of idiopathic pulmonary fibrosis: A case report.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a special form of spontaneous, chronic, progressive interstitial fibrotic pneumonia of unknown cause, and treatments for IPF have shown a poor prognosis. This study reports a new treatment, traditional Chinese medicine (TCM) therapy, for tonifying Qi-deficiency of lung-kidney in a 64-year-old patient with IPF. PATIENT CONCERNS: A 64-year-old man, who complained of cough and asthma, was diagnosed as IPF with mild impairment in lung function by thoracic high-resolution computed tomography and pulmonary function test. He received an 18-month N-acetylcysteine monotherapy but had no improvement in lung function. DIAGNOSES: IPF with mild impairment in lung function was diagnosed. INTERVENTIONS: The Chinese herbal medicine composition was decocted in 300 ml water for oral administration with 150 ml decoction twice daily in June 2017. OUTCOMES: The pulmonary function test showed that diffusing capacity for carbon monoxide had increased to 81% of predicted back to normal after 2-month TCM monotherapy. And diffusing capacity for carbon monoxide had increased to 89% of predicted, and forced expiratory volume in 1 s/forced vital capacity ratio increased to 92% at 14-month follow-up. No adverse events occurred during the 14 months of therapy and observation. LESSONS: The treatment by TCM therapy of tonifying lung-kidney's Qi-deficiency for IPF can improve the pulmonary function and reverse disease progression; it may be considered as a complementary treatment for IPF with mild-to-moderate impairment. However, the insights provided in this case report require further exploration and verification.

Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial.

BACKGROUND: The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. METHODS: We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients. RESULTS: In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. CONCLUSION: This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.

Clinical use of evidence-based medicine--clinical questions: Acetylcysteine, a new treatment for an old foe?

This is a small, good quality, randomized controlled trial that shows a modest slowing in the deterioration of VC and DLco with the addition of high dose N-acetylcysteine to standard therapy in IPF. Overall the study should be interpreted with caution given its high drop out rate, which may have biased the results towards a more dramatic slowing of the disease progression. There were no differences in dyspnea score or functional status. There was no increase in the adverse events in the N-acetylcysteine group and the medication is inexpensive. Given only modest effects of N-acetylcysteine on VC and DLco, no change in functional scores, and the flaws of the study we would hesitate to use N-acetylcysteine as standard therapy in all patients with IPF.

High-dose acetylcysteine in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added to standard therapy with prednisone plus azathioprine. The primary end points were changes between baseline and month 12 in vital capacity and in single-breath carbon monoxide diffusing capacity (DL(CO)). RESULTS: A total of 182 patients were randomly assigned to treatment (92 to acetylcysteine and 90 to placebo). Of these patients, 155 (80 assigned to acetylcysteine and 75 to placebo) had usual interstitial pneumonia, as confirmed by high-resolution computed tomography and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment. Fifty-seven of the 80 patients taking acetylcysteine (71 percent) and 51 of the 75 patients taking placebo (68 percent) completed one year of treatment. Acetylcysteine slowed the deterioration of vital capacity and DL(CO): at 12 months, the absolute differences in the change from baseline between patients taking acetylcysteine and those taking placebo were 0.18 liter (95 percent confidence interval, 0.03 to 0.32), or a relative difference of 9 percent, for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal (95 percent confidence interval, 0.27 to 1.23), or 24 percent, for DL(CO) (P=0.003). Mortality during the study was 9 percent among patients taking acetylcysteine and 11 percent among those taking placebo (P=0.69). There were no significant differences in the type or severity of adverse events between patients taking acetylcysteine and those taking placebo, except for a significantly lower rate of myelotoxic effects in the group taking acetylcysteine (P=0.03). CONCLUSIONS: Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL(CO) in patients with idiopathic pulmonary fibrosis better than does standard therapy alone.

Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study.

OBJECTIVE: Iloprost is a stable prostacyclin analogue which has been shown to be effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the effects of long-term cyclic therapy with iloprost in comparison with nifedipine on the skin score, pulmonary function and Raynaud's severity score in patients with SSc and RP. METHODS: We conducted a 12-month prospective, randomised, parallel-group, blind-observer trial to compare the effects of intravenously infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day and subsequently for 8 hours on one day every 6 weeks) with those of conventional vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc and RP. RESULTS: At 12 months, iloprost but not nifedipine reduced the skin score (iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from 10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016) and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02 vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value, worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/- 6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2 +/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). CONCLUSION: In SSc patients, cyclic intravenous iloprost infusion is able to control vasospastic disease. Our results suggest that it might also act as a disease-modifying agent, as it seems to improve the course of the disease. Further studies principally focused on organ involvement and the natural history of the disease are needed to confirm our results.

Effects of nifedipine on diffusing capacity and pulmonary capillary blood volume in chronic obstructive pulmonary disease. A controlled study.

The acute dose-dependent effects of nifedipine on the pulmonary diffusing capacity for CO and other lung function indices were investigated in patients with chronic obstructive pulmonary disease (COPD) in a randomized double-blind, cross-over, placebo-controlled trial. Seventeen successive, clinically stable, moderate COPD patients with pulmonary hypertension and 15 control subjects were included in the study. The diffusing capacity of the lungs for carbon monoxide (DLCO) was measured with the single-breath method. Nifedipine (10 and 20 mg) and placebo were administered sublingually at room air. Nifedipine (10 and 20 mg) increased DLCO and DLCO/alveolar volume; however, a larger effect was observed with 10 mg. In addition, nifedipine increased the pulmonary capillary blood volume dose-dependently while arterial oxygenation was improved only with 10 mg nifedipine. Venous shunt was significantly increased with 20 mg nifedipine whereas spirometric parameters were unaffected. The percent DLCO change with 10 or 20 mg nifedipine was inversely correlated with baseline DLCO, but not with the severity of obstruction. Nifedipine did not have any effect in the control group, except for mild hypotension and a reflex increase in the heart rate. It is concluded that 10 mg nifedipine probably has an effect on the pulmonary circulation in moderate COPD patients with pulmonary hypertension.

Dynamic pulmonary arterial hypertension: a new form of pulmonary hypertension in patients with impaired pulmonary diffusing capacity due to toxic oil syndrome.

The authors studied the pulmonary haemodynamic response to exercise in eleven patients with toxic oil syndrome (TOS) (mean age 38.3 +/- 15.7 years; 10 women, 1 man) and abnormal pulmonary diffusing capacity (39.1 +/- 10.3% of predicted value) without clinical evidence of pulmonary hypertension. Eight patients had normal pulmonary pressure at rest (mean PAP less than 25 mmHg) and three showed mild pulmonary hypertension. After exercise the mean PAP rose to 35.3 +/- 11.5 mmHg from a basal value of 20.72 +/- 3.8 mmHg (p less than 0.01). Only four patients did not develop pulmonary hypertension during exercise. Pulmonary artery oxygen saturation decreased from 72.9 +/- 1.9% at rest to 52.3 +/- 10.1% during exercise (p less than 0.01). In conclusion, in this subset of TOS patients, an early diagnosis of their subclinical pulmonary hypertension can be made on the basis of the presence of dyspnoea and abnormal pulmonary diffusing capacity for carbon monoxide and can be then confirmed with the exercise haemodynamic test.

[Effect of a single dose of nifedipine on the CO transfer capacity in patients with scleroderma]. / Effet d'une prise unique de nifédipine sur la capacité de transfert du CO de patients sclérodermiques.

The calcium antagonists are currently used in the treatment of Raynaud's syndrome for patients with scleroderma. The effect on the pulmonary vasculature in these patients is little understood. The study reported here is based on 15 patients with scleroderma. In each patient lung volumes, expiratory flow and transfer factor (DLCO) were carried out in a basal state and one hour after the administration of sub lingual nifedipine. Nine patients showed a diminution in the DLCO before taking the product but the mean variation after nifedipine was not significant. Different mechanisms may explain the absence of any effect: irreversible vascular disease or the absence of pulmonary arterial hypertension or hypoxic constriction, the latter conditions were previously associated with the efficacy of nifedipine. Thus it does not seem that nifedipine, in acute tests, has an effect on the pulmonary localisation of scleroderma, at least in the absence of pulmonary arterial hypertension.

Silicosis in workers dealing with tonoko: case reports and analyses of tonoko.

We found three cases of pneumoconiosis among those workers who had been dealing with tonoko (a mineral powder) for more than ten years at a shop making wooden furniture in Sendai, Japan. In the factory the workers were exposed to tonoko dust and had been inhaling it for a long time. Until now, this disease has not been found in employees of furniture factories; and, furthermore, tonoko has not been regarded as a harmful material. Tonoko is a very fine mineral powder used widely in Japan for filling the grains of surfaces of wooden products. The three workers had scanty clinical symptoms; however, their chest x-ray films revealed disseminated nodulations throughout both pulmonary fields. One of the workers suffered from the complication of active pulmonary tuberculosis. Some of the analyses revealed that tonoko contained about 50% quartz. Accordingly, the disease is strongly suspected to be a sort of silicosis caused by inhalation of tonoko dust.