Treatment Of Interstitial Pneumonia Research Articles

Effect of the new silicon-based agent on the symptoms of interstitial pneumonitis

Interstitial pneumonia (IP) is a collective term for diseases whose main lesion is fibrosis of the pulmonary interstitium, and the prognosis associated with acute exacerbation of these conditions is often poor. Therapeutic agents are limited to steroids, immunosuppressants, and antifibrotic drugs, which and have many side effects; therefore, the development of new therapeutic agents is required. Because oxidative stress contributes to lung fibrosis in IP, optimal antioxidants may be effective for the treatment of IP. Silicon (Si)-based agents, when administered orally, can continuously generate a large amount of antioxidant hydrogen in the intestinal tract. In this study, we investigated the effect of our Si-based agent on methotrexate-induced IP, using the IP mouse models. Pathological analysis revealed that interstitial hypertrophy was more significantly alleviated in the Si-based agent-treated group than in the untreated group (decreased by about 22%; P < 0.01). Moreover, additional morphological analysis demonstrated that infiltration of immune cells and fibrosis in the lungs were significantly inhibited by treatment with the Si-based agent. Furthermore, Si-based agent reduced oxidative stress associated with IP by increasing blood antioxidant activity. (increased by about 43%; P < 0.001). Taken together, these results suggest that Si-based agents can be effective therapeutic agents for IP.

The role of pirfenidone in the treatment of interstitial pneumonia with autoimmune features.

No approved pharmacotherapies are available for patients with interstitial pneumonia with autoimmune features (IPAF). In the present work, we aimed to evaluate the efficacy and safety of pirfenidone for the treatment of IPAF. A retrospective cohort study consisting of patients who met diagnostic criteria for IPAF was performed after a multidisciplinary review, and the patients receiving pirfenidone were compared with those in the non-pirfenidone group. The baseline data and diagnostic characteristics of patients were assessed. Pulmonary function and prednisone dose were analysed by a mix-effects model. A total of 184 patients, who met the diagnostic criteria of IPAF, were divided into two groups: pirfenidone group (n=81) and non-pirfenidone group (n=103). Patients in the pirfenidone group had a lower forced vital capacity (FVC%, p<0.001) and a lower diffusion capacity for carbon monoxide (DLCO%, p=0.003). The pirfenidone group exhibited a greater increase of FVC% at 6 (p=0.003), 12 (p=0.013), and 24 (p=0.003) months. After adjustment for sex, age, UIP pattern, baseline FVC% and DLCO%, patients in the pirfenidone group continued to show a greater improvement in FVC% (χ2(1)=4.59, p=0.032). Subgroup analysis identified superior therapeutic effects of pirfenidone in patients with dosage >600 mg/day (p=0.010) and medication course >12 months (p=0.007). Besides, the pirfenidone group had a lower prednisone dose than the non-pirfenidone group after 12 months of treatment (p=0.002). Moreover, 17 patients (19.32%) experienced side effects after taking pirfenidone, including one case of anaphylactic shock. Pirfenidone (600-1,800 mg/day) might help improve FVC, with an acceptable safety and tolerability profile in IPAF patients.

Prophylactic antibiotic treatment with TMP-SMX decreased the incidence of interstitial pneumonia in patients with B-cell lymphoma on chemotherapy

BackgroundSeveral studies have reported the incidence of interstitial pneumonia (IP) among patients with non-Hodgkin lymphoma (NHL) that are undergoing combination chemotherapy plus rituximab; however, the effective prophylactic treatment for IP remains unclear. This study aims to explore the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) on IP and identify IP-associated risk factors in NHL patients.MethodsBetween March 2013 and April 2018, 498 patients (264 males, 53%) with B-cell NHL undergoing first-line RCHOP-like chemotherapy treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone were enrolled in this study.ResultsThese patients had a median age of 56 years, and 311 of the 498 patients (62.4%) were administered once daily with the prophylactic treatment of TMP-SMX. IP occurred in 65 patients (13.1%), indicating a significant reduction in the IP incidence rate (21.4% vs. 8.0%; p < 0.001). Among patients treated with TMP-SMX, 2 (1.2%) exhibited rashes, 38 (12.2%) suffered from nausea and vomiting, 52 (16.7%) showed signs of neutropenia, and 18 (5.8%) suffered from kidney dysfunction. Both univariate and multivariate analysis showed that gender (male), history of diabetes, and absence of prophylactic TMP-SMX treatment were significant risk factors associated with IP. Disease progression was observed in 55/311 (17.7%) patients that underwent prophylactic TMP-SMX treatment and in 63/187 (33.7%) patients that did not (p < 0.001).ConclusionsThis study revealed that the occurrence of IP was common in B-cell NHL patients undergoing combined chemotherapy plus rituximab treatment. IP could be reduced with prophylactic treatment of once-daily oral TMP-SMX.

Successful treatment with endoscopic transpapillary drainage for gallbladder perforation associated with steroid treatment for interstitial pneumonia (with video).

This case report highlights the clinical efficacy of endoscopic transpapillary drainage for gallbladder perforation in a high-risk surgical patient with a history of steroid treatment for interstitial pneumonia. The usefulness of endoscopic transpapillary gallbladder drainage in high-risk surgical patients with acute cholecystitis has not been established. In difficult cases of emergent surgery, such as described here, endoscopic transpapillary drainage is a promising method to manage gallbladder perforation and acute cholecystitis recurrence.

Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19: A proposal for a multi-centric prospective trial

BackgroundCOVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. Study design and methodsThis multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function.This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48–72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators.Trial registration: ClinicalTrial.gov NCT-04380818 https://clinicaltrials.gov/ct2/show/NCT04380818?term=RADIOTHERAPY&cond=COVID&draw=2&rank=4.

Effects of CX3CL1 inhibition on murine bleomycin-induced interstitial pneumonia

Background:Treatment for interstitial pneumonia (IP) associated with collagen diseases has not been established. There is a need to elucidate the pathogenesis of IP and develop a novel therapy. We aimed to clarify the role of chemokine (C-X3-C motif) ligand 1 (CX3CL1, also known as fractalkine) in IP.Methods:Bleomycin (BLM) was intratracheally administered to C57BL/6 mice to induce IP. For treatment with control Ab or anti-CX3CL1 mAb, the mice were administered either Ab three times per week for 2 weeks from the day of BLM administration until euthanasia. Expressions of CX3CL1 and its unique receptor CX3CR1 in the lung tissue were examined by immunohistochemical analysis. Cellular infiltration and lung fibrosis were evaluated based on hematoxylin-eosin-staining and Sirius red staining of the lung tissue sections, respectively. Bronchoalveolar lavage fluid (BALF) cells were analyzed by flow cytometry.Results:CX3CL1 and CX3CR1 were strongly expressed in the lung tissue from mice with BLM-induced IP (BLM-IP). Treatment with anti-CX3CL1 mAb did not significantly alter inflammatory cell infiltration or fibrosis in the lung tissue. However, the number of M1-like macrophages in BALF was decreased and surface CD3 expression on T cells was increased by anti-CX3CL1 mAb treatment.Conclusions:Inhibition of CX3CL1 decreased inflammatory cells and may attenuate T cell activation in BALF. CX3CL1 inhibitor may have the potential to suppress the infiltration and activation of immune cells in IP.

4. Recent Progress in Diagnosis and Treatment of Interstitial Pneumonias

4. Recent Progress in Diagnosis and Treatment of Interstitial Pneumonias

全身性強皮症による間質性肺炎の治療経過中に発症し肺炎類似の画像所見を呈した肺小細胞癌の1例

全身性強皮症による間質性肺炎の治療経過中に発症し肺炎類似の画像所見を呈した肺小細胞癌の1例

Treatment of interstitial pneumonia in autoimmune mice with cyclosporin A

Treatment of interstitial pneumonia in autoimmune mice with cyclosporin A

Breakthrough disseminated zygomycosis induced massive gastrointestinal bleeding in a patient with acute myeloid leukemia receiving micafungin

A 69-year-old man, who had been receiving prednisolone for 11 months for treatment of interstitial pneumonia, was diagnosed with acute myeloid leukemia. During induction therapy, he developed severe pneumonia. Although meropenem and micafungin were started, he died of circulatory failure owing to massive gastrointestinal bleeding. Autopsy specimens obtained from the stomach revealed fungal hyphae, which had invaded diffusely into submucosal vessels and caused the massive gastric bleeding. The same hyphae were also observed in both lungs. A diagnosis of disseminated zygomycosis was confirmed by its characteristic histopathological findings. Because zygomycetes are spontaneously resistant to the newer antifungal agents, such as voriconazole or micafungin, it seems likely that the prevalence of zygomycosis as a breakthrough infection may increase in the future. Zygomycosis is a rare, but life-threatening, deep fungal infection that appears in immunologically or metabolically compromised hosts. Its manifestations are clinically similar to those of invasive aspergillosis. In addition to the well-established epidemiology of zygomycosis, this case suggests the following new characteristics. (1) Although the gastrointestinal manifestation of zygomycosis is relatively rare, it is observed more frequently than invasive aspergillosis. (2) Gastrointestinal zygomycosis occasionally leads to the development of necrotic ulcers and may induce hemorrhagic shock.(3) We should be cautious of an occurrence of breakthrough zygomycosis when we use echinocandins for patients with known risk factors, especially steroid use and neutropenia. (4) For patients who are receiving broad-spectrum antibiotics and echinocandins, who are negative for culture studies and aspergillus antigen, and who present with unresolved fever, it is important to make a prompt clinical diagnosis of zygomycosis.

3. Diagnosis and Treatment of Interstitial Pneumonia

3. Diagnosis and Treatment of Interstitial Pneumonia

Step-up versus primary intensive approach to the treatment of interstitial pneumonia associated with dermatomyositis/polymyositis: a retrospective study

Corticosteroids (CS) are the standard initial treatment for interstitial pneumonia (IP) associated with dermatomyositis (DM)/polymyositis (PM). However, many patients fail to respond and have significantly high mortality even if immunosuppressive drugs (ISDs) are subsequently added, while a more intensive initial approach using ISDs is suggested to improve their survival. We conducted a retrospective study to examine the association between initial therapeutic approaches and clinical outcomes of active IP in DM/PM patients. We reviewed medical records of 34 consecutive DM/PM patients who had active IP defined by the presence of pulmonary function abnormality or active symptoms, and compared clinical outcome between those patients to whom ISDs were added if CS alone did not result in a favorable response (a step-up approach) and those who were started on ISDs simultaneously with CS (a primary intensive approach). Clinical endpoints were death, pulmonary death, and progression or improvement of pulmonary function. The step-up approach was used in 20 patients, to 11 of whom ISDs were eventually added after a median of 2.0 weeks, while the primary intensive approach was used in 14 patients. The primary intensive approach group had significantly better survival than the step-up approach group (P = 0.030 by the log-rank test). These two groups did not differ significantly in demographic characteristics and baseline clinical and laboratory features. Intensive approach by starting ISDs simultaneously with CS in the initial treatment for active IP in DM/PM patients was associated with better survival, emphasizing the impact of initial treatment on their survival. Prospective clinical investigation of this approach is now needed, but the limited clinical utility of CS as an initial treatment might ethically challenge clinical-trial designing.

Step-up versus primary intensive approach to the treatment of interstitial pneumonia associated with dermatomyositis/polymyositis: a retrospective study

Corticosteroids (CS) are the standard initial treatment for interstitial pneumonia (IP) associated with dermatomyositis (DM)/polymyositis (PM). However, many patients fail to respond and have significantly high mortality even if immunosuppressive drugs (ISDs) are subsequently added, while a more intensive initial approach using ISDs is suggested to improve their survival. We conducted a retrospective study to examine the association between initial therapeutic approaches and clinical outcomes of active IP in DM/PM patients. We reviewed medical records of 34 consecutive DM/PM patients who had active IP defined by the presence of pulmonary function abnormality or active symptoms, and compared clinical outcome between those patients to whom ISDs were added if CS alone did not result in a favorable response (a step-up approach) and those who were started on ISDs simultaneously with CS (a primary intensive approach). Clinical endpoints were death, pulmonary death, and progression or improvement of pulmonary function. The step-up approach was used in 20 patients, to 11 of whom ISDs were eventually added after a median of 2.0 weeks, while the primary intensive approach was used in 14 patients. The primary intensive approach group had significantly better survival than the step-up approach group (P = 0.030 by the log-rank test). These two groups did not differ significantly in demographic characteristics and baseline clinical and laboratory features. Intensive approach by starting ISDs simultaneously with CS in the initial treatment for active IP in DM/PM patients was associated with better survival, emphasizing the impact of initial treatment on their survival. Prospective clinical investigation of this approach is now needed, but the limited clinical utility of CS as an initial treatment might ethically challenge clinical-trial designing.

A Case of Splenic Abscess during Treatment of Interstitial Pneumonia

A Case of Splenic Abscess during Treatment of Interstitial Pneumonia

Cyclosporin Treatment in Steroid-resistant and Acutely Exacerbated Interstitial Pneumonia

The aim of this study was to evaluate the efficacy of cyclosporin A (CsA) in patients with interstitial pneumonia (IP). Retrospective comparative study. We reviewed 33 patients (23 males and 10 females with a mean age of 62.5 years) with histologically-proven progressive IP who were treated with CsA. All patients had corticosteroid-resistant IP or developed acute exacerbation of IP in their courses. The underlying systemic diseases were: idiopathic interstitial pneumonias (IIPs) in 19 patients, and collagen vascular diseases (CVDs) in 14. The histopathological patterns and underlying diseases of IP were classified as usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) in 10 patients, cellular-nonspecific interstitial pneumonia (NSIP)/IIPs in 3, fibrotic-NSIP/IIPs in 5, organizing pneumonia (OP)/IIP in 1, UIP/CVDs in 4, cellular-NSIP/CVDs in 7, fibrotic-NSIP/CVDs in 2, and diffuse alveolar damage (DAD)/CVD in 1, respectively. They received a low dosage of CsA combined with corticosteroids. The prognoses after treatment with CsA were well correlated with histopathological patterns. Cellular-NSIP and OP showed better prognoses than fibrotic-NSIP, UIP or DAD. In addition, CVDs had better prognoses than IIPs, when compared on the basis of the same histopathological patterns. Furthermore, the prognoses in the CsA-treated group were significantly better than in those without CsA treatment in regard to acute exacerbation of UIP/IPF. CsA combined with corticosteroids may be an efficacious treatment for corticosteroid-resistant IP and for acute exacerbation of IPF.

Clinical analysis of interstitial pneumonia after surgery for lung cancer

The postoperative development or exacerbation of interstitial pneumonia (IP) in lung cancer patients often affects prognoses. We analyzed the patients who suffered from IP after surgery, to determine treatment and prevention of IP. One hundred and one consecutive patients who underwent resection were enrolled in the study. Clinical background and post-, perioperative course were compared between patients who developed IP and those who did not. If IP developed or was exacerbated, steroid pulse (SP) therapy, immunosuppressant (IS) therapy or nitric oxide (NO) inhalation therapy was employed. Of 101 patients, 20 had suffered from IP before surgery. In four of these 20 (20%), postoperative exacerbation was observed. SP therapy was given to all patients. To one patient, IS and NO therapy were added. Three of the four patients died. 81 patients did not have IP; three of them (3.7%) developed IP after the operation and were treated with SP therapy. To one patient, IS and NO therapy were added. Two of the three patients died. IP development or exacerbation after surgery was observed in seven of 101 patients, and five of them died. It was significantly more frequent in patients with poorly differentiated squamous cell carcinoma, restrictive change in pulmonary function tests, and a low percentage diffusion capacity for carbon monoxide. Postoperative development or exacerbation was observed in patients who had undergone lobectomy or pneumonectomy. Postoperative IP is a serious complication. Further studies are needed to determine definitive therapeutic options. For the patients with the aforementioned risk factors, limited surgery must be considered.

Medical treatment for interstitial pneumonia of collagen disease.

Medical treatment for interstitial pneumonia of collagen disease.