Inhibiting TGF-[Formula: see text] 1-Mediated Cellular Processes as an Effective Strategy for the Treatment of Pulmonary Fibrosis with Chinese Herbal Medicines.

Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease that even threatens the lives of some patients infected with COVID-19. PF is a multicellular pathological process, including the initial injuries of epithelial cells, recruitment of inflammatory cells, epithelial-mesenchymal transition, activation and differentiation of fibroblasts, etc. TGF-[Formula: see text]1 acts as a key effect factor that participates in these cellular processes of PF. Recently, much attention was paid to inhibiting TGF-[Formula: see text]1 mediated cell processes in the treatment of PF with Chinese herbal medicines (CHM), an important part of traditional Chinese medicine. Here, this review first summarized the effects of TGF-[Formula: see text]1 in different cellular processes of PF. Then, this review summarized the recent research on CHM (compounds, multi-components, single medicines and prescriptions) to directly and/or indirectly inhibit TGF-[Formula: see text]1 signaling (TLRs, PPARs, micrRNA, etc.) in PF. Most of the research focused on CHM natural compounds, including but not limited to alkaloids, flavonoids, phenols and terpenes. After review, the research perspectives of CHM on TGF-[Formula: see text]1 inhibition in PF were further discussed. This review hopes that revealing the inhibiting effects of CHM on TGF-[Formula: see text]1-mediated cellular processes of PF can promote CHM to be better understood and utilized, thus transforming the therapeutic activities of CHM into practice.

Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury and Pulmonary Fibrosis in Mice.

We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as indices of lung function and bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed for biomarkers of fibrosis. Mice on phytoestrogen-free diet demonstrated increased mortality and stronger signs of chronic lung injury and pulmonary fibrosis, as reflected in the expression of collagen, extracellular matrix deposition, histology, and lung mechanics, compared to mice on regular diet. We conclude that dietary phytoestrogens play an important role in the pathogenesis of pulmonary fibrosis and suggest that phytoestrogens (e.g., genistein) may be useful as part of a therapeutic regimen against hydrochloric acid-induced lung fibrosis and chronic lung dysfunction.

Antifibrotic action of Yifei Sanjie formula enhanced autophagy via PI3K-AKT-mTOR signaling pathway in mouse model of pulmonary fibrosis.

Pulmonary fibrosis (PF) is a crippling disease characterized by progressive dyspnea and associated with a high mortality rate, but its origin is unknown and there is no effective treatment. Yifei Sanjie formula (YFSJF) is a Chinese medicine that is widely used for treatment of respiratory systems disease. However, the molecular basis for the function of YFSJF has not been determined. Here we investigate the contribution of YFSJF in BLM-induced PF mice. Administration with YFSJF significantly alleviated the degree of BLM-induced collagen I and III deposition and the inflammatory injuring in the lungs and suppressed hydroxyproline release in PF animals. The active components of YFSJF are comprised with flavonoid, amino acids, saponins, oligosaccharide, organic acid, vitamin, esters, purine nucleosides. Additionally, there was a significant increase in autophagosomes, after treatment with YFSJF in PF animals. Interestingly, autophagy dysfunction by the blocker chloroquine (CQ) resulted in collagen deposition and inducing the expression of fibrosis-related genes. In addition, YFSJF-induced autophagy is mediated by the PI3K-AKT-mTOR pathway, and knockdown of PI3K by siRNA up-regulated the expression of autophagy-related genes and down-regulated the expression of collagen in human lung fibroblasts (HLF). Our findings provide a detailed understanding that YFSJF-antifibrotic effects are mainly mediated by triggering autophagy, and suppressing phosphorylation of the PI3K-AKT-mTOR pathway is required for YFSJF-curative effect.

Protective Effect of Selenium-L-methionine on Radiation-induced Acute Pneumonitis and Lung Fibrosis in Rat.

BACKGROUND: In this study, we aimed to detect the changes in the level of interleukin (IL)-4 and IL-13 cytokines and their downstream genes including interleukin-13 receptor subunit alpha-2 (IL13Ra2), interleukin-4 receptor subunit alpha-1 (IL4Ra1), dual oxidase 1 (DUOX1) and dual oxidase 2 (DUOX2). The protective effects of Selenium-L-methionine on radiation-induced histopathological damages and changes in the level of these cytokines and genes were detected. METHODS: Four groups of 20 rats (5 rats in each) namely, control; Selenium-L-methionine, radiation and radiation plus Selenium-L-methionine were used in this study. 4 mg/kg of Selenium-Lmethionine was administered 1 day before irradiation and five consecutive days after irradiation. Irradiation was done using a dose of 15 Gy 60Co gamma rays at 109 cGy/min. All rats were sacrificed 10 weeks after irradiation for detecting changes in IL-4 and IL-13 cytokines, the expressions of IL13Ra2, IL4Ra1, Duox1 and Duox2 and histopathological changes. RESULTS: The level of IL-4 but not IL-13 increased after irradiation. This was associated with increased expression of IL4Ra1, Duox1 and Duox2, in addition to changes in morphological properties. Selenium-L-methionine could attenuate all injury markers following lung irradiation. CONCLUSION: Selenium-L-methionine can protect lung tissues against toxic effects of ionizing radiation. It is possible that the modulation of immune responses and redox interactions are involved in the radioprotective effect of this agent.

Protective effect of hydroxysafflor yellow A on bleomycin- induced pulmonary inflammation and fibrosis in rats.

OBJECTIVE: To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflflammation and pulmonary fibrosis induced by bleomycin (BLM) in rats. METHODS: Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone (DXM) group. Three doses of HSYA (35.6, 53.3, and 80.0 mg•kg-1•day-1) were intraperitoneally (i.p.) injected in rats for 3 weeks after BLM administration and DXM was used as the positive control (n=8 or 12). Arterial blood gas was assayed and morphological changes were observed. Lung mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin (α-SMA) protein distribution in rat lung tissue was observed by immunohistochemistry. RESULTS: On the 7th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure (PaO2) increased (HSYA 80.0 mg•kg-1, P<0.01) and CO2 partial pressure (PaCO2) decreased (HSYA 53.3, 80.0 mg•kg-1, P<0.05). Moreover, the mRNA expression of TNF-α, IL-1ß, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg•kg-1 groups than those in the model group (all P<0.05). Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO2 (HSYA 53.3, 80.0 mg•kg-1, P<0.01), and decreased PaCO2 (53.3 and 80.0 mg•kg-1, P<0.05). Further, the mRNA expression of TGF-ß1, α-SMA, and collagen I as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes (53.3, 80.0 mg•kg-1, P<0.05). Hematoxylin and eosin and Masson's trichrome staining indicated that the fibrosis and collagen deposition were ameliorated in HSYA groups (53.3, 80.0 mg•kg-1, P<0.05). CONCLUSION: HSYA could alleviate acute lung inflflammation and chronic pulmonary fibrosis induced by BLM in rats.

Effect of Xinjiang Uyghur Vernonia anthelmintica Willd Injection Treatment with Silicosis Fibrosis.

Objective. To observe the curative effect of VAWI on Xinjiang Uygur patients with silicosis fibrosis. Methods. After we diagnosed the 40 patients with the first phase of silicosis, we randomly divided them into two groups: the basic treatment group (group A, n = 20) and the VAWI group (group B, n = 20). At the same time, we selected the age-matched healthy patients (n = 20). We applied the combined protein chip with SELDI-TOF-MS to carry out the serum analysis. The data were analyzed throughout data preprocessing, difference in PEAK screening, hierarchical cluster analysis, and Principal Component Analysis (PCA). We built decision tree model and predict the difference between the PEAK corresponding proteins. Results. The proteins peaks corresponding to name, predicted protein, and gene name were as follows: M2001_69, amyloid beta a4 protein, APP, and M2017_02, amyloid beta a4 protein, APP. The different expression of proteins in patients with silicosis was found before and after with VAWI treatment. The predicted proteins were as follows: M1982_50, amyloid beta a4 protein, APP; M3164_50, fibrinogen alpha chain frag, FGA; M3379_28, fibrinogen alpha chain frag, FGA; and so on. Conclusion. VAWI presented curative effect on patients with silicosis fibrosis via the alternation of proteins expression in serum.

Polyacrylate/nanosilica causes pleural and pericardial effusion, and pulmonary fibrosis and granuloma in rats similar to those observed in exposed workers.

Nanomaterials offer great benefit as well as potential damage to humans. Workers exposed to polyacrylate coatings have pleural effusion, pericardial effusion, and pulmonary fibrosis and granuloma, which are thought to be related to the high exposure to nanomaterials in the coatings. The study aimed to determine whether polyacrylate/silica nanoparticles cause similar toxicity in rats, as observed in exposed workers. Ninety male Wistar rats were randomly divided into five groups with 18 rats in each group. The groups included the saline control group, another control group of polyacrylate only, and low-, intermediate-, and high-dose groups of polyacrylate/nanosilica with concentrations of 3.125, 6.25, and 12.5 mg/kg. Seventy-five rats for the 1-week study were terminated for scheduled necropsy at 24 hours, 3 days, and 7 days postintratracheal instillation. The remaining 15 rats (three males/group) had repeated ultrasound and chest computed tomography examinations in a 2-week study to observe the pleural and pericardial effusion and pulmonary toxicity. We found that polyacrylate/nanosilica resulted in pleural and pericardial effusions, where nanosilica was isolated and detected. Effusion occurred on day 3 and day 5 post-administration of nanocomposites in the 6.25 and 12.5 mg/kg groups, it gradually rose to a maximum on days 7-10 and then slowly decreased and disappeared on day 14. With an increase in polyacrylate/nanosilica concentrations, pleural effusion increased, as shown by ultrasonographic qualitative observations. Pulmonary fibrosis and granuloma were also observed in the high-dose polyacrylate/nanosilica group. Our study shows that polyacrylate/nanosilica results in specific toxicity presenting as pleural and pericardial effusion, as well as pulmonary fibrosis and granuloma, which are almost identical to results in reported patients. These results indicate the urgent need and importance of nanosafety and awareness of toxicity of polyacrylate/nanosilica.

Acupuncture Treatment for Dyspnea due to Combined Pulmonary Fibrosis and Emphysema: A Case Report.

OBJECTIVE: Combined idiopathic pulmonary fibrosis with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. Dyspnea on exertion (DOE) is a major symptom of CPFE. We report a patient with DOE due to CPFE who was successfully treated with acupuncture. DESIGN: Case report. CASE PRESENTATION: A 72-year-old Japanese man with a 4-year history of DOE was diagnosed with CPFE 2 years previously in another hospital. He received standard Western medicine treatment, which included bronchodilators. However, his DOE did not improve. Consequently, he visited our hospital for acupuncture treatment and received acupuncture treatment once a week for 1 year. RESULTS: After 10 weeks of acupuncture treatment, the results of the 6-minute walk test (6-minute walking distance, 379 m; lowest oxygen saturation, 86%; modified Borg dyspnea scale score: 2 units) were better than those at baseline (352 m, 84%, 4 units, respectively). These values were sustained at both 30 weeks (470 m, 88%, 1 unit) and 60 weeks (473 m, 85%, 2 units). Serum interstitial biomarkers, Krebs von den Lungen and surfactant protein-D, decreased after commencement of acupuncture therapy. CONCLUSION: A patient with CPFE showed improvements in dyspnea scores, exercise tolerance, and serum biomarkers during a 1-year course of acupuncture treatment. Use of acupuncture might be an effective adjunct therapy in relieving DOE due to CPFE. A large, well-designed cohort study that includes patients with CPFE treated with acupuncture should be conducted.

Rikkunshito ameliorates cachexia associated with bleomycin-induced lung fibrosis in mice by stimulating ghrelin secretion.

Cachexia is a frequent complication in patients with respiratory failure, such as lung fibrosis, and it is a determining factor for functional capacity, health status, and mortality. Reductions in body weight and skeletal muscle mass are key features of cachexia that are resistant to current therapies. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment for patients with gastrointestinal symptoms and known to stimulate ghrelin secretion. By using bleomycin (BLM)-induced lung fibrosis mice in this study, we tested our hypothesis that RKT administration could ameliorate pulmonary cachexia. After BLM administration, mice were provided with either RKT or distilled water on a daily basis. Compared with the BLM-injected mice, the RKT-treated mice had smaller reductions of food intake and body weight. Skeletal muscle weights were retained in the RKT-treated mice, in conjunction with reduced expressions of MuRF-1 and atrogin-1 in the lysates of skeletal muscle found in lung fibrosis. Rikkunshito administration restored the plasma concentrations of ghrelin in BLM-injected mice. The anticachectic efficacies of RKT administration in BLM-injected mice were canceled by the concurrent treatment of a ghrelin receptor antagonist. Rikkunshito administration did not decrease the degree of loss of body weight or food intake reduction in either ghrelin-deficient mice or growth hormone secretagogue receptor-deficient mice. Our results indicate that RKT administration exerts protective effects on pulmonary cachexia by ameliorating skeletal muscle wasting and food intake reduction as mediated by the ghrelin system and, thus, highlight RKT as a potential therapeutic agent for the management of lung fibrosis.

Clinical case: Combined pulmonary fibrosis and emphysema with pulmonary hypertension--clinical management.

BACKGROUND: Combined idiopathic pulmonary fibrosis (IPF) with pulmonary emphysema (CPFE) is a syndrome with a characteristic presentation of upper lobe emphysema and lower lobe fibrosis. While CPFE is a strong determinant of secondary precapillary pulmonary hypertension (PH), there is limited evidence regarding the management of patients with CPFE and PH. CASE PRESENTATION: A 63 year-old male presented in 2006 with dyspnoea on exertion having quit smoking in 2003. Clinical examination, together with high resolution computed tomography, bronchoalveolar lavage, and echocardiographic assessments, suggested a diagnosis of CPFE without PH. In 2007, the patient received intravenous cyclophosphamide, N-acetylcysteine, and short-term anticoagulation treatment. Due to remission of acute exacerbations, the patient received triple combination therapy (prednisone, N-acetylcysteine and azathioprine). Upon progressive clinical worsening, long-term supplemental oxygen therapy was initiated in 2009. Repeated right heart catheterisation in 2011 confirmed PH and worsening pulmonary haemodynamics, and off-label ambrisentan therapy was initiated. Dyspnoea remained at follow-up, although significant haemodynamic improvement was observed. CONCLUSION: CFPE is a distinct but under-recognized and common syndrome with a characteristic presentation. Further studies are needed to ascertain the etiology, morbidity, and mortality of CPEF with or without PH, and to evaluate novel management options.

La relación entre el reflujo gastroesofágico y las enfermedades de la vía aérea: el paradigma del reflujo a vía aérea / Relationship Between Gastro-Oesophageal Reflux and Airway Diseases: The Airway Reflux Paradigm

Nuestro conocimiento sobre la relación entre el reflujo gastroesofágico (RGE) y las enfermedades respiratoriasha conllevado recientemente a cambios importantes. El paradigma previo del reflujo a vía aérea(RVA) o RGE que llega hasta la vía aérea como sinónimo de la enfermedad por reflujo gastroesofágicoclásica (ERGE) con la pirosis como síntoma imprescindible ha sido definitivamente rechazado. Numerososestudios epidemiológicos han mostrado una asociación altamente significativa entre el reflujo ácido,líquido y gaseoso de la ERGE con condiciones tales como enfermedades laríngeas, rinosinusitis crónica,asma resistente al tratamiento, EPOC e inclusive fibrosis pulmonar idiopática. Hoy se sabe que graciasa estudios del síndrome de hipersensibilidad tusígena gran parte del reflujo que llega a la vía aérea noes diagnosticado debido a su escaso o nulo contenido de ácido o a su composición gaseosa. La evidenciapara esta relación se basa en la historia clínica que se˜nala una asociación sintomática con factores precipitantesconocidos del reflujo. Las exploraciones para el diagnóstico del RA no poseen la sensibilidado la reproducibilidad que han demostrado las del reflujo esofágico de la ERGE. Desafortunadamente, elacceso a la metodología para la detección de tal reflujo empezó a ser posible hace muy poco tiempo y serequiere aún muchos trabajos de investigación para perfilar correctamente su papel(AU)

Our understanding of the relationship between gastro-oesophageal reflux and respiratory disease hasrecently undergone important changes. The previous paradigm of airway reflux as synonymous withthe classic gastro-oesophageal reflux disease (GORD) causing heartburn has been overturned. Numerousepidemiological studies have shown a highly significant association of the acid, liquid, and gaseousreflux of GORD with conditions such as laryngeal diseases, chronic rhinosinusitis, treatment resistantasthma, COPD and even idiopathic pulmonary fibrosis. However, it has become clear from studies oncough hypersensitivity syndrome that much reflux of importance in the airways has been missed, sinceit is either non- or weakly acid and gaseous in composition. The evidence for such a relationship relieson the clinical history pointing to symptom associations with known precipitants of reflux. The tools forthe diagnosis of extra-oesophageal reflux, in contrast to the oesophageal reflux of GORD, lack sensitivityand reproducibility. Unfortunately, methodology for detecting such reflux is only just becoming availableand much additional work is required to properly delineate its role(AU)

Frequency of atrial flutter after adult lung transplantation.

Lung transplantation, which involves an anastomosis of the graft to the native left atrium, may increase the risk of left-side atrial flutter (AFL). Our aim was to evaluate the incidence, predisposing conditions, and course of AFL after lung transplantation in adults. Two hundred sixty-nine consecutive patients who underwent lung transplantation were studied retrospectively. All patients received a preoperative echocardiogram and postoperative electrocardiographic monitoring. All 12-lead electrocardiograms were reviewed. Typical or atypical AFL was diagnosed by 2 independent reviewers based on accepted criteria. Predictors of AFL were investigated separately using univariate and multivariate logistic regression analyses. AFL occurred in 35 of 269 patients (13%) over a mean of 12 days after transplantation. All patients who developed AFL had no previous atrial arrhythmia. Of these 35 patients, 24 (68.6%) had atypical AFL by electrocardiographic criteria. In multivariate logistic regression analysis, patients with idiopathic pulmonary fibrosis (IPF) were 2.9 times more likely to have AFL than those patients with lung transplant without IPF (p = 0.009). Other independent risk factors for AFL were advanced age and preoperative left atrial enlargement. Only 3 of 35 patients (8.6%) with AFL had persistent atrial arrhythmia and needed electrophysiologic study and ablation. In conclusion, AFL is common soon after lung transplantation. Those with IPF, advanced age, or left atrial enlargement are at increased risk. In most cases, AFL is a self-limited arrhythmia that resolves spontaneously with no need for ablation.

[Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis with inspiratory muscle training]. / Rehabilitacja oddechowa chorych z idiopatycznym sródmiazszowym wlóknieniem pluc za pomoca programu z cwiczeniami miesni wdechowych.

INTRODUCTION: Evaluation of effectiveness of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis (IPF) has not yet been presented in medical literature. The objective of the study is to analyze the influence of inspiratory muscle training on dyspnea (oxygen cost diagram [OCD], baseline dyspnea index [BDI]), quality of life (SF-36), results of 6 MWT (distance, dyspnea in Borg's scale), maximal inspiratory pressure (MIP), and lung function tests (IC, TLC, VC, FEV1, DLCO(SB), DLCO/VA) in patients with IPF. MATERIAL AND METHODS: Investigations were conducted before, after 6 and 12 weeks of pulmonary rehabilitation performed in 2 groups of patients: study group (GB)--16 patients--with inspiratory muscle training added to general body conditioning and in control group (GK)--14 patients--who performed only general body conditioning. RESULTS: After 12 weeks of rehabilitation in SG we noticed the significant decrease of dyspnoea before (p = 0.028) and after (p = 0.012) 6 MWT, increase of distance in 6 MWT (p = 0.001), increase of MIP (p = 0.006), decrease of dyspnoea in BDI (p = 0.001) and improvement of quality of life (SF-36/PCS; p = 0.030) in comparison to baseline values. In the GK we observed increase of distance in 6MWT (p = 0.001) and improvement in quality of life (SF-36/PCS; p = 0.016). No improvement in sensation of dyspnea during 6MWT, BDI and MIP was noticed in the GK. CONCLUSION: Adding inspiratory muscle training increases effectiveness of pulmonary rehabilitation in IPF patients.

[Intractable pneumothorax successfully treated by talc slurry pleurodesis and video-assisted thoracoscopic surgery in a patient with idiopathic pulmonary fibrosis].

Pneumothorax associated with idiopathic pulmonary fibrosis (IPF) is intractable and often fatal because the patients are usually under a long-term steroid therapy, and are associated with severely impaired lung function. Further, pneumothorax itself recurs frequently, and acute exacerbation of IPF may develop after a surgical intervention. Here, we describe a case of intractable pneumothorax developed in a patient with IPF who was successfully treated with repeated talc pleurodesis combined with video-assisted thoracoscopic surgery under local anesthesia. A 67-year-old male with IPF who was under a long-term treatment with steroid, developed right-sided pneumothorax. A chest drainage tube was placed in the right pleural cavity, and repeated pleurodesis with minocycline or fibrinogen was challenged, but the outcome turned out to be unsuccessful. Then, talc slurry was applied repeatedly, resulting in a high-grade fever associated with reactive accumulation of pleural effusion. However, air leakage did not cease completely despite the eight-times pleurodesis with talc using 16 g in total. Finally, video-assisted thoracoscopic surgery under local anesthesia was undertaken and the pulmonary fistula was successfully closed.

[Fatal acute exacerbation of idiopathic pulmonary fibrosis/usual interstitial pneumonia initially in the right lung after surgery lobectomy for left lung cancer].

A tumor was found in the left S10 in a chest CT scan of a 72-year-old male patient with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP). He underwent left lower lobectomy and resection of the hilar and mediastinal lymph nodes under video-assisted thoracoscopic surgery. The histopathological evaluation disclosed a well-differentiated squamous cell carcinoma (T1N0M0; stage IA) associated with UIP. On the sixth postoperative day, a severe hypoxemia (PaO2 48 mmHg) developed, and the chest CT showed diffuse ground glass opacity (GGO) in the right lung. A diagnosis of acute exacerbation of IPF/UIP was made, and steroid pulse therapy with cyclosporin A was started. However, despite this therapy, the diffuse GGO extended to both lung fields, and the patient died of respiratory failure 82 days later. The histopathology at autopsy demonstrated diffuse alveolar damage due to UIP that was consistent with acute exacerbation of IPF/UIP. It is suggested that the acute exacerbation of IPF/UIP could have been triggered by a high concentration of oxygen or mechanical lung injury during the patient's surgery.

A study of the cough reflex in idiopathic pulmonary fibrosis.

Little is known about the pathogenesis of cough in idiopathic pulmonary fibrosis (IPF). We hypothesized that abnormalities of respiratory tract tachykinin-containing sensory nerves may be implicated. We studied cough response to capsaicin, substance P (SP), and bradykinin in 10 healthy control subjects and 10 patients with IPF. Six patients were tested before and after steroid therapy. Induced sputum cell counts and neurotrophic factor levels were also measured in 13 patients and 13 control subjects. The results show that cough sensitivity to capsaicin was greater in patients (p < 0.01). Neither SP nor bradykinin induced cough in normal subjects. SP and bradykinin induced cough in 7/10 patients (p < 0.002) and 2/10 patients (not significant) with IPF, respectively. Prednisolone caused a reduction in cough sensitivity to capsaicin (p < 0.05) and SP (p < 0.05) in all six patients treated. There were significantly more neutrophils (p = 0.001) and higher levels of nerve growth factor (p < 0.01) and brain-derived neurotrophic factor (p < 0.01) in patient's sputa. These findings suggest functional upregulation of lung sensory neurones in IPF. The cough response to inhaled SP in most patients may reflect disrupted respiratory epithelium. The response to corticosteroids demonstrates that the cough is amenable to therapy.

Complex regional pain syndrome type I after myocardial infarction treated with spinal cord stimulation.

OBJECTIVE: A rare case of Complex Regional Pain Syndrome (CRPS) type I after myocardial infarction (MI) and significant comorbid illness with few treatment options for pain control was successfully managed with the placement of a spinal cord stimulator (SCS). CASE REPORT: A 44-year-old man presented with left upper extremity burning pain after MI. His past medical history included insulin-dependent diabetes mellitus, oxygen-dependent idiopathic pulmonary fibrosis, and recent coronary revascularization surgery. His pain was presumed to be related to his MI and a clinical diagnosis of CRPS type I (or reflex sympathetic dystrophy) was made. Facing limited medical and less invasive options for his pain relief, he underwent a spinal cord stimulation trial with excellent response. He had more than 70% pain relief from the spinal cord stimulation at the last follow-up, 2 years later. CONCLUSION: CRPS type I after MI can be difficult to treat because of other comorbid illnesses. SCS can be a safe and effective mode of therapy for patients facing limited treatment options.

Dyspnea assessment and management in hospice patients with pulmonary disorders.

Accurate assessments and appropriate management of dyspnea are essential to provide improved quality of life for hospice patients. This study describes methods of assessing dyspnea and interventions used to manage dyspnea in 72 hospice patients with end-stage lung disease or lung cancer. The mean age of the sample was 72.46 years old and the majority was white (80 percent) and male (62 percent). Paired t-tests were used to compare mean scores on admission and near death for dyspnea severity, Karnofsky functional status, pain, and Mini-Mental Status scores. Results showed significant decline in functional and cognitive status, but no significant changes in dyspnea severity and pain. Dyspnea was often assessed subjectively with observational methods only. Use of inhalants, oxygen, positioning, steroids, and oral opioids were the most frequent therapies for dyspnea. Relaxation, guided imagery, and other complementary therapies were rarely used (five percent or less). Measurement of dyspnea needs to be done frequently by using standardized instruments to assess severity and degree of symptom distress as well as the effects of treatment. Clinical trials are needed to determine which dyspnea interventions are most effective in terminally ill patients. Guidelines such as those developed for pain management are needed for effectively managing dyspnea.

High-dose therapy and autologous transplantation in amyloidosis-AL.

A 53-yr.-old woman with amyloidosis AL was treated with high-dose chemotherapy and autologous stem cell infusion in an attempt to suppress the amyloid secretion. A diagnosis of MGUS had been made six years earlier. During the last year her disease had progressively shifted to a full-blown picture of amyloidosis AL, with renal failure, proteinuria, renal amyloid deposition and plasma cell sheets in the marrow. After an unsuccessful attempt with standard-dose chemotherapy, she received a high-dose regimen of busulphan (14 mg/Kg) and melphalan (40 mg/m2), followed by the infusion of both autologous bone marrow and peripheral blood stem cells. She had full and prompt engraftment, but eight weeks post-graft developed interstitial pneumonitis: CMV was isolated. The patient died while in the intensive care unit. In the literature, this is the first case of amyloidosis AL treated with high-dose therapy and autologous transplantation.

Short- and long-term hemodynamic effects of oral nifedipine in patients with pulmonary hypertension secondary to COPD and lung fibrosis. Deleterious effects in patients with restrictive disease.

STUDY OBJECTIVE: The present study was undertaken to evaluate at rest the short- and long-term effects of oral nifedipine (N) in patients with pulmonary hypertension (PH). DESIGN AND SETTING: A prospective study with ten consecutive cases during two years in a setting of a district acute hospital. PATIENTS OR PARTICIPANTS: Seven patients with advanced COPD and three with severe lung fibrosis (LF) during a period of stable condition. Three patients with COPD were eligible for the long-term investigation. INTERVENTIONS: Right heart catheterization with a 7F Swan-Ganz triple-lumen thermodilution catheter and radial cannulation with a 3F arterial catheter. MEASUREMENTS AND RESULTS: Measurement of CO, MAP, RAP, PAP, PWP, HR, and ABG and calculation of CI, TSR, PAR, and DO2 before and after 20 mg of N sublingually at rest. For the group as a whole, N induced a reduction in MAP and TSR, with a significant increase in CI and DO2. There were no significant changes in PAP, PAR (magnitude of the reduction: -10 percent), HR, and PaO2. The individual analysis of the driving pressures (PAP-PWP) in function of the cardiac output demonstrated that a real vasodilating effect in the pulmonary circulation occurred in only three COPD patients (magnitude of the PAR reduction: -43 percent), while in the three patients with LF, N induced a deleterious increase in PAP and PAR. After long-term treatment (10 mg of N daily every 4 h; average 12 months) in the former, despite a persistent beneficial hemodynamic effect (magnitude of the PAR reduction: -36 percent), there was the usually expected clinical worsening. CONCLUSIONS: N in small doses may be able in some patients with severe COPD to induce a beneficial short- and long-term hemodynamic effect on the pulmonary circulation when PH is present. On the other hand, N should not be used in patients with PH and advanced LF.