The Chinese herb Tripterygium wilfordii Hook F for the treatment of systemic sclerosis-associated interstitial lung disease: data from a Chinese EUSTAR Center.

OBJECTIVE: To assess the efficacy and safety of the Chinese herb Tripterygium wilfordii Hook F (TwHF) for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: SSc-ILD patients who were regularly treated for more than 1 year and were currently taking a stable dose of TwHF (40-60 mg/day) or CYC (100 mg/day) were selected from the EUSTAR database of Peking Union Medical College Hospital. The efficacy of treatments was assessed by the change in pulmonary function, including the forced vital capacity (FVC) and the percentage of predicted FVC (FVC pred%). RESULTS: Among the 431 patients diagnosed with SSc-ILD, 76 fulfilled the inclusion and exclusion criteria. Twenty eight patients received TwHF monotherapy, while 48 received oral CYC monotherapy. Baseline data prior to treatment did not differ significantly between the two groups. After 1 year of treatment, significant improvements in the FVC and FVC pred% were seen in both groups (P < 0.05) and the magnitude of improvement was comparable (P = 0.93). However, TwHF was only found to be effective in improving FVC and FVC pred% when administered as a maintenance therapy, but not as an induction therapy. No severe adverse events were seen in either group. Leucopenia occurred more often in the CYC group compared to the TwHF group (P = 0.034). CONCLUSION: TwHF may be considered as a potential alternative drug for SSc-ILD patients, especially as a maintenance therapy. A prospective randomized controlled trial is necessary to further confirm these results.Key Points• This is the first clinical study of Tripterygium wilfordii Hook F (TwHF) in the treatment of SSc-ILD, providing a novel therapeutic option for SSc-ILD.• TwHF shows a comparable therapeutic efficacy to CYC when treating SSc-ILD.• TwHF has unique therapeutic advantages considering the balance of economy and safety and may be a good potential choice for maintenance therapy.

Effects of Pursed Lip Breathing on Exercise Capacity and Dyspnea in Patients With Interstitial Lung Disease: A RANDOMIZED, CROSSOVER STUDY.

BACKGROUND: Although mainly described in patients with chronic obstructive pulmonary disease, pursed lip breathing (PLB) could prove useful in patients with interstitial lung disease (ILD) by improving exertional tachypnea and respiratory control. This prospective, randomized, crossover trial aimed at evaluating the impact of PLB on dyspnea and walking distance in ILD patients. METHODS: ILD patients with total lung capacity of <80% predicted were randomized to 6-min walk tests using either PLB or usual breathing. Patients were crossed over for the second 6-min walk tests and served as their own controls. Ventilatory and metabolic variables were recorded using a portable metabolic cart and were compared at 1-min intervals. RESULTS: Thirty-five patients were included (mean forced vital capacity of 64 ± 10% predicted). Use of PLB resulted in lower mean respiratory rates and larger tidal volumes (both P < .001), worsened dyspnea ratings (post-6-min walk test Borg score: 5.2 ± 2.6 vs 4.2 ± 2.3, P < .001), and walking distance (403 ± 102 m vs 429 ± 93 m, P < .001). Twenty-nine patients (83%) described PLB as less comfortable than usual breathing. Both groups had similar total ventilation and oxygen saturation (all P > .05), but PLB resulted in higher mean oxygen uptake (13.9 ± 3.6 vs 12.9 ± 3.2 mL/kg/min, P = .02), even when corrected for walking distance (P < .001). CONCLUSION: In ILD patients, acute exposure to PLB did not improve exertional dyspnea, walking distance, or gas exchange, and was associated with higher metabolic demands than usual breathing. These results cast doubt on the usefulness of this technique in ILD patients and should be taken into account when tailoring pulmonary rehabilitation programs to this population.

Systems medicine advances in interstitial lung disease.

Fibrotic lung diseases involve subject-environment interactions, together with dysregulated homeostatic processes, impaired DNA repair and distorted immune functions. Systems medicine-based approaches are used to analyse diseases in a holistic manner, by integrating systems biology platforms along with clinical parameters, for the purpose of understanding disease origin, progression, exacerbation and remission.Interstitial lung diseases (ILDs) refer to a heterogeneous group of complex fibrotic diseases. The increase of systems medicine-based approaches in the understanding of ILDs provides exceptional advantages by improving diagnostics, unravelling phenotypical differences, and stratifying patient populations by predictable outcomes and personalised treatments. This review discusses the state-of-the-art contributions of systems medicine-based approaches in ILDs over the past 5 years.

Heterogeneity of lung disease associated with NK2 homeobox 1 mutations.

We retrospectively studied the clinical presentation, treatment modalities and outcome in 16 patients with heterozygous NKX2-1 mutation associated with chronic lung disease. Twelve different NKX2-1 mutations, including 4 novel mutations, were identified in the 16 patients. Nine patients presented with brain-lung-thyroid syndrome, 3 had neurological and lung symptoms and 4 had only pulmonary symptoms. Ten patients had neonatal respiratory distress, and 6 of them developed infiltrative lung disease (ILD). The other patients were diagnosed with ILD in childhood (n = 3) or in adulthood (n = 3). The median age at diagnosis was 36 months (IQ 3.5-95). Patient testing included HRCT (n = 13), BALF analysis (n = 6), lung biopsies (n = 3) and lung function tests (n = 6). Six patients required supplemental oxygen support with a median duration of 18 months (IQ 2.5-29). All symptomatic ILD patients (n = 12) benefited from a treatment consisting of steroids, azithromycin (n = 9), and/or hydroxychloroquine (n = 4). The median follow-up was 36 months (IQ 24-71.5). One patient died of respiratory failure at 18 months and another is waiting for lung transplantation. In summary, the initial diagnosis was based on clinical presentation and radiological features, but the presentation was heterogeneous. Definitive diagnosis required genetic analysis, which should be performed, even in absence of neurological or thyroid symptoms.

Predictive factors for long-term outcome in polymyositis/dermatomyositis-associated interstitial lung diseases.

BACKGROUND: Interstitial lung disease (ILD) is strongly associated with polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM). It is also related to mortality. Previous studies have highlighted that the acute form of PM/DM/CADM-associated ILD (PM/DM/CADM-ILD) has a poor short-term prognosis. However, little is known about the long-term clinical features of patients with PM/DM/CADM-ILD. The aim of the present study is to clarify the clinical characteristics and the predictive factors for long-term outcomes in patients with PM/DM/CADM-ILD. METHODS: Thirty-four patients with PM/DM/CADM-ILD who were followed up for more than 12 months were analyzed retrospectively. The patients were classified as "stable" or "deterioration" according to respiratory symptoms, serial changes in forced vital capacity (FVC) or arterial oxygen pressure, and radiologic findings during the follow-up period. RESULTS: Twenty-six patients (76%) were in the stable group and eight patients (24%) were in the deterioration group. Home oxygen therapy was performed in six cases in the deterioration group because of chronic respiratory failure due to progression of ILD. The deterioration group, in comparison to the stable group, had a significantly lower %FVC and a higher positive rate for the anti-PL-7 antibody. Multivariate logistic regression analysis revealed that a positive anti-PL-7 antibody test and a lower %FVC were independently associated with deterioration during long-term follow-up. CONCLUSIONS: Patients with PM/DM/CADM-ILD are at risk for chronic respiratory failure due to the deterioration of ILD during long-term follow-up. The presence of anti-PL-7 antibody and a lower %FVC at initial diagnosis may predict long-term deterioration in patients with PM/DM/CADM-ILD.

Papel de la vitamina D en enfermedad pulmonar obstructiva crónica, asma y otras enfermedades respiratorias / The Role of Vitamin D in Chronic Obstructive Pulmonary Disease, Asthma and Other Respiratory Diseases

En los últimos años existe un creciente interés por las acciones extraóseas de la vitamina D. En este artículo revisamos la fisiología de la vitamina D, los aspectos fisiopatológicos asociados a su déficit y la evidencia existente sobre su papel etiopatogénico en enfermedades respiratorias. Teniendo en cuenta las acciones pleiotrópicas de la vitamina D, existe plausibilidad biológica sobre un potencial papel patogénico del déficit de esta vitamina en el desarrollo de diversas enfermedades respiratorias. Sin embargo, los numerosos estudios epidemiológicos que han encontrado asociación entre niveles bajos de vitamina D y mayor riesgo de desarrollar diversas enfermedades respiratorias o de conllevar un peor pronóstico no permiten demostrar causalidad. Los análisis post hoc de algunos ensayos clínicos, especialmente en enfermedad pulmonar obstructiva crónica (EPOC) y asma, parecen demostrar que ciertos subtipos de pacientes podrían beneficiarse de la corrección del déficit de vitamina D. En este sentido, resultará interesante averiguar si las variantes genéticas implicadas en el metabolismo de la vitamina D pueden explicar las diferencias interindividuales encontradas en cuanto al efecto del déficit de vitamina D y la respuesta a su corrección. En último término, solo los ensayos clínicos adecuadamente diseñados permitirán determinar si los suplementos de 25-OH D pueden tener un efecto preventivo o mejorar la evolución de las distintas enfermedades respiratorias en las que se ha descrito asociación epidemiológica entre su pronóstico y el déficit de esta vitamina

There has been a growing interest in recent years in the extraosseous effects of vitamin D. In this article, we review the physiology of vitamin D, the physiopathological effects associated with vitamin D deficit and the available evidence on its etiopathogenic role in respiratory diseases. Given the pleiotropic actions of vitamin D, it is biologically plausible that the deficit of this vitamin could play a pathogenic role in the development of various respiratory diseases. However, the many epidemiological studies that have shown an association between low vitamin D levels and a higher risk of developing various respiratory diseases, or a poorer prognosis if they do appear, were unable to show causality. Post hoc analyses of some clinical trials, particularly in chronic obstructive pulmonary disease (COPD) and asthma, appear to suggest that some patient subtypes may benefit from correction of a vitamin D deficit. In this respect, it would be interesting to determine if the interindividual differences found in the effect of vitamin D deficit and responses to correcting this deficit could be explained by the genetic variants involved in vitamin D metabolism. Ultimately, only appropriately designed clinical trials will determine whether 25-OH D supplements can prevent or improve the course of the various respiratory diseases in which an epidemiological association between prognosis and vitamin D deficit has been described

Supportive care for patients with pulmonary complications of connective tissue disease.

Patients with connective tissue disease often suffer from pulmonary complications, including interstitial lung disease and pulmonary hypertension. Supportive care for these patients aims to relieve symptoms and improve activity level and quality of life. A holistic approach to the management of patients with advanced connective tissue disease-associated pulmonary disorders includes a full assessment of patient symptoms as well as a careful search for side effects of treatment and treatable comorbidities. This article addresses supportive measures such as supplemental oxygen and pulmonary rehabilitation. Issues related to quality of life, sleep disturbances, and identification of mood disorders are discussed. In addition, we review significant comorbidities, including cardiovascular disease, glucocorticoid-induced osteoporosis, and gastroesophageal reflux disease. Essential facets of advanced lung disease, including mechanical ventilation, lung transplantation, end-of-life care, and hospice, are covered.

Long-term N-acetylcysteine therapy in systemic sclerosis interstitial lung disease: a retrospective study.

Systemic sclerosis (SSc) is associated with interstitial lung diseases. The primary endpoints of this study were changes between baseline and month 24 in single-breath carbon monoxide diffusing capacity (DLco). The secondary endpoints were: vital capacity (VC), forced expired volume in 1 sec (FEV1), total lung capacity (TLC), scores of high resolution computed tomography (HRCT) of the chest, number of adverse effects. In this study, we retrospectively investigated data from SSc patients who had undergone therapy with high-dose intravenous N-acetylcysteine (NAC) at a dosage of 15 mg/Kg/h for 5 consecutive hours every 14 days. After NAC therapy median values of DLco (69.5 vs 77.7%), VC (99 vs 101.3%) and TLC (93 vs 98.3%) significantly increased. We did not observe any significant changes from baseline in FEV1 value and HRTC score. The improvement in lung function was more evident in SSc patients without radiological signs of pulmonary fibrosis than in patients with pulmonary fibrosis. In SSc patients with mild-moderate pulmonary fibrosis intravenous NAC administration slows the rate of deterioration of DLco, VC and TLC. In conclusion, this retrospective study demonstrates that long-term therapy with intravenous NAC ameliorates pulmonary function tests in SSc patients.

Catheter ablation of atrial fibrillation in patients with chronic lung disease.

BACKGROUND: Chronic lung disease (CLD) is one of the important underlying diseases of atrial fibrillation (AF). The outcomes after radiofrequency catheter ablation of AF in patients with CLD have not yet been reported. We investigated the electroanatomic alterations in pulmonary veins (PVs) in CLD patients with AF and assessed their effect on the outcomes of radiofrequency catheter ablation of AF. METHOD AND RESULTS: We assessed 15 patients who had CLD and underwent radiofrequency catheter ablation of AF. CLD included chronic obstructive pulmonary disease, a tuberculosis-destroyed lung, and interstitial lung disease. For controls, we selected 60 sex-, age-, and procedure era-matched non-CLD patients who received radiofrequency catheter ablation for AF (4 controls for each CLD patient). Eight patients had chronic obstructive pulmonary disease, 6 had a tuberculosis-destroyed lung, and 1 had interstitial lung disease. PV morphology in the affected lung was altered significantly, ie, obliteration, pulling of the PVs toward the destroyed lung, or compensatory bulging of the PV antrum. These alterations were related to arrhythmogenicity in 6 (40%) of 15 patients with CLD. Non-PV foci were more common in the CLD group (4/15, 26.7%) than in the control group (3/60, 5.0%; P=0.025). All non-PV foci were located in the right atrium. The AF recurrence rate in the CLD group (26.7%, 4/15) was similar to that in the control group (18.3%, 11/60; P=0.45). CONCLUSIONS: Significant alteration of PV anatomy was related to arrhythmogenicity, and non-PV foci from the right atrium were commonly observed in the CLD group. Radiofrequency catheter ablation can be performed safely for AF in CLD patients with a comparable success rate to that in patients with normal lungs.

A combination of intravenous immunoglobulin and pulse methylprednisolone extended survival in pulmonary alveolar proteinosis with chronic interstitial pneumonitis: a case report.

Pulmonary alveolar proteinosis (PAP) is characterized by intra-alveolar accumulation of lipoproteinaceous material. The severe chronic pulmonary disease and susceptibility to pulmonary infection is a prominent feature of the disease. We reported a case of postnatal-onset PAP and chronic interstitial pneumonitis in a girl with chronic respiratory distress since she was 5 months of age. A lung biopsy confirmed the diagnosis. The therapeutic bronchoalveolar lavages, a short trial of granulocyte colony-stimulation factor (G-CSF) and a combination of low dose methylprednisolone and hydroxychloroquine were used at different times without noting satisfactory improvement. Intravenous immunoglobulin (IVIG) and pulse methylprednisolone were given monthly with gradual recovery. She did not require oxygen supplement after 21 months of this combination. Our report suggested that IVIG and pulse methylprednisolone might have a potential role in the treatment of PAP with chronic interstitial pneumonitis.

Interstitial pneumonia probably associated with sorafenib treatment: An alert of an adverse event.

There has been no literature which reports a case of interstitial lung disease associated with sorafenib. However, a recent post-marketing survey in Japan revealed that interstitial pneumonia occurred in 4 among approximately 2 000 Japanese patients treated with sorafenib. In this article, we describe a Japanese patient with severe interstitial pneumonia probably caused by sorafenib treatment for metastatic renal cell carcinoma. Oncologists supervising future clinical trials for lung cancer should be alert to the fact that sorafenib can potentially induce serious interstitial lung disease, although this might depend on racial differences.

Management of interstitial lung disease in systemic sclerosis: lessons from SLS and FAST.

Interstitial lung disease (ILD) is a leading cause of death in systemic sclerosis (SSc). Two randomized controlled trials recently demonstrated the modest effects of cyclophosphamide on lung physiology (forced vital capacity) and extrapulmonary outcomes (dyspnea, function, quality of life, and skin thickening). Recommendations can now be made about the short-term management for SSc-ILD. However, many questions remain unanswered, including how long to treat with cyclophosphamide; whether patients should take maintenance therapy after the initial or induction phase; whether there are alternative therapies; how to treat patients with ILD and pulmonary hypertension; and how to treat patients with severe ILD.

Dyspnea and quality of life in patients with pulmonary fibrosis after six weeks of respiratory rehabilitation.

The aim of the study was to estimate the level of dyspnea and quality of life in patients with pulmonary fibrosis after 6 weeks' respiratory rehabilitation. The study comprised of 31 patients (F/M-12/19) with interstitial lung diseases (21 with idiopathic interstitial pneumonia, 4 with lung fibrosis due to allergic alveolitis, 4 with lung fibrosis due to collagenosis, 2 with lung fibrosis due to silicosis) who successfully finished the rehabilitation program. Each patient underwent an intensive (every day for 30 min) inpatient pulmonary rehabilitation program of an average length of 4 wk, continued later at home for up to 12 wk. The program consisted of respiratory muscle training and bicycle riding to the limits of the patient's tolerance. Dyspnea (MRC, OCD, BDI and Borg scale) and the quality of live (SF-36, St. George's Respiratory Questionnaire) were assessed at the time of admission and discharge. Rehabilitation caused dyspnea sensation to diminish (Borg scale: 2.97 before vs. 2.19 after). Some domains of the quality of life in SF-36 questionnaire (Role-Physical 40.6 vs. 60.2) and St. George's Respiratory Questionnaire (activity: 52 vs. 45, impact 47 vs. 40 and total 47 vs. 42) also were improved compared with the pre-rehabilitation results. We conclude that 12 weeks of combined inpatient and home-based rehabilitation programme improves the quality of live and sensation of dyspnea in patients with interstitial lung disease, despite changes in pulmonary function tests.