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Biomedical subjects

A P Perruchoud

Publications and source records attributed to A P Perruchoud.

At least 19 recordsLinked to original sources

The use of B-type natriuretic peptide in the management of patients with diabetes and acute dyspnoea.

AIMS/HYPOTHESIS: The aim of this study was to determine the impact of measurement of B-type natriuretic peptide (BNP) levels on the management of patients with diabetes presenting with acute dyspnoea. METHODS: This study evaluated the subgroup of 103 patients with diabetes included in the B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL) study (n=452). Patients were randomly assigned to a diagnostic strategy with (n=47, BNP group) or without (n=56, control group) the use of BNP levels assessed by a rapid bedside assay. Time to discharge and total cost of treatment were recorded as the primary endpoints. RESULTS: Although similar with regard to age and sex, patients with diabetes more often had pre-existing cardiovascular and renal disease and heart failure as the cause of acute dyspnoea compared with patients without diabetes. In addition, medical and economic outcomes were worse in patients with diabetes. The use of BNP levels significantly reduced time to discharge (median 9 days [interquartile range (IQR) 2-16] in the BNP group vs 13 days [IQR 8-22] in the control group; p=0.016). At 30 days, the diabetic patients in the BNP group had spent significantly fewer days in hospital compared with the diabetic patients in the control group (9 days [IQR 2-19] vs 16 days [IQR 8-24], respectively; p=0.008). Total treatment costs at 30 days were US$5,705 (IQR 2,285-9,137) in the BNP group and US$7,420 (IQR 4,194-11,966) in the control group (p=0.036). CONCLUSIONS/INTERPRETATION: The results of this study indicate that measurement of BNP levels improves the management of patients with diabetes presenting with acute dyspnoea.

Acute Disease↗

Right bundle branch block and long-term mortality in patients with acute congestive heart failure.

OBJECTIVES: Risk stratification in acute congestive heart failure (ACHF) is poorly defined. The aim of the present study was to assess the impact of right bundle brunch block (RBBB) on long-term mortality in patients presenting with ACHF. METHODS AND RESULTS: The initial 12-lead electrocardiogram was analysed for RBBB in 192 consecutive patients presenting with ACHF to the emergency department. The primary endpoint was all-cause mortality during 720-day follow-up. This study included an elderly cohort (mean age 74 years) of ACHF patients. RBBB was present in 27 patients (14%). Age, sex, B-type natriuretic peptide levels and initial management were similar in patients with RBBB when compared with patients without RBBB. However, patients with RBBB more often had pulmonary comorbidity. A total of 84 patients died during follow-up. Kaplan-Meier analysis revealed that mortality at 720 days was significantly higher in patients with RBBB when compared with patients without RBBB (63% vs. 39%, P = 0.004). In Cox proportional hazard analysis, RBBB was associated with a two-fold increase in mortality (hazard ratio 2.18, 95% CI 1.26-3.66; P = 0.003). This association persisted after adjustment for age and comorbidity. CONCLUSIONS: RBBB is a powerful predictor of mortality in patients with ACHF. Early identification of this high-risk group may help to offer tailored treatment in order to improve outcome.

Aged↗

Coronary artery disease and outcome in acute congestive heart failure.

OBJECTIVES: To quantify the prognostic impact of coronary artery disease (CAD) on patients with acute heart failure (HF). DESIGN: Prospective cohort study of 217 consecutive patients presenting with acute HF to the emergency department. Treatment, hospitalisation, the use of revascularisation procedures, and survival were observed during follow up of up to three years. RESULTS: CAD was present in 153 patients (71%). Patients with and without CAD were similar with respect to age and sex. Although adequate HF treatment was initiated more rapidly among patients with CAD, their initial outcomes including hospitalisation rate, time to discharge, and total treatment cost were significantly worse. Moreover, despite higher use of angiotensin converting enzyme inhibitors and beta blockers during follow up, patients with CAD had a significantly lower survival rate. Cumulative survival at 720 days was 48.7% of patients with CAD as compared with 76.4% of patients without CAD (p = 0.0004). In Cox regression analysis the presence of CAD increased the risk of death by more than 250% (hazard ratio 2.57, 95% confidence interval 1.50 to 4.39, p = 0.001). This strong association persisted after multivariate adjustments. The use of coronary angiography and coronary revascularisation procedures was low, both at initial presentation and during follow up. CONCLUSION: CAD is a strong and independent predictor of mortality among patients with acute HF. Whether, for example, less restrictive use of revascularisation procedures in this elderly HF population can improve the outcome for patients with CAD warrants further study.

Acute Disease↗

Collagenase expression and activity is modulated by the interaction of collagen types, hypoxia, and nutrition in human lung cells.

Hypoxia not only controls organogenesis, embryogenesis, and wound repair, but also triggers tumor progression and metastasis. Matrix metalloproteinases (MMP), especially gelatinases (MMP-2, MMP-9) regulate the composition and stability of the extracellular matrix (ECM), which affects cell proliferation, migration, and differentiation. This study investigated the effect of hypoxia alone and in combination with ECM compounds and nutrition on MMP-2 and MMP-9 expression, activity, and synthesis in human lung fibroblasts and pulmonary vascular smooth muscle cells (VSMC). We also determined the expression of the tissue inhibitors of MMP (TIMP-1, -2). Cells were grown on plastic, collagen-I, collagen-IV, or gelatin and in either starving medium (0.1% serum) or growth medium (5% serum), and were subjected to normoxia or hypoxia (1% O(2)). Collagenases expression was determined by zymography. TIMP-1, -2 expression was assessed by Western blotting and RT-PCR. Depending on serum concentration human lung cells expressed pro-MMP-2 on all substrates. Hypoxia increased pro-MMP-2 expression, on collagen type I or type IV further via Erk1/2 and p38 MAP kinase signaling. MMP-9 was only expressed when cells were grown on collagen type IV and increased with serum concentration, and by hypoxia. TIMP-1 expression was only expressed when cells were grown on collagen type I and was significantly increased by hypoxia, while TIMP-2 expression was unchanged. We demonstrated that the hypoxia, ECM composition, and nutrition, rather than one of these conditions alone, modulate the expression and activity of collagenases and their inhibitors in primary human lung fibroblasts.

Cells, Cultured↗

Use of pro-atrial natriuretic peptide in the detection of myocardial ischaemia.

BACKGROUND: Because of its unique storage and release mechanisms allowing a very rapid response to haemodynamic changes, pro-atrial natriuretic peptide (proANP) may be a helpful cardiac marker in the detection of myocardial ischaemia. MATERIALS AND METHODS: A total of 260 consecutive patients with suspected myocardial ischaemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography (SPECT) were enrolled. Levels of plasma proANP were determined before and 1 min after maximal exercise. RESULTS: Baseline proANP and peak exercise proANP were significantly higher in patients with myocardial ischaemia as compared to those without ischaemia (median, 82 [IQR, 57-112] vs. 67 [IQR, 50-106] pmol L(-1), P = 0.007; and 89 [IQR, 65-121] vs. 78 [IQR, 57-116] pmol L(-1), P = 0.033). The area under the ROC curve for baseline proANP was 0.597 (95% CI, 0.527-0.667), as compared to 0.577 (95% CI, 0.507-0.648) for peak exercise proANP. Exercise-induced changes in proANP were similar in patients with and without myocardial ischaemia, and showed no correlation with the extent of myocardial ischaemia. CONCLUSIONS: Baseline proANP and peak exercise proANP are significantly higher in patients with myocardial ischaemia. However, because of considerable overlap in proANP levels between patients with and without myocardial ischaemia, neither measurement seems helpful in the detection of myocardial ischaemia in clinical practice.

Aged↗

The use of B-type natriuretic peptide in the management of elderly patients with acute dyspnoea.

OBJECTIVES: The aim of this study was to define the impact of B-type natriuretic peptide (BNP) levels on the management of elderly patients presenting with acute dyspnoea. DESIGN: We performed a prospective randomized controlled study in 269 elderly patients at least 70 years of age included in the B-type natriuretic peptide for Acute Shortness of breath Evaluation (BASEL) study. Patients were randomly assigned to a diagnostic strategy with (n = 136, BNP group) or without (n = 133, control group) the use of BNP levels provided by a rapid bedside assay. The time to discharge and the total cost of treatment were the primary end-points. RESULTS: Amongst elderly patients, baseline characteristics were well matched between both groups. The use of BNP levels significantly reduced the time to discharge (median 9.0 in the BNP group versus 11.0 days in the control group; P = 0.029). Total treatment cost was $5381 (95% CI, 4482-6280) in the BNP group when compared with $7411 (95% CI, 6180-8642; P = 0.009) in the control group. In addition, a significant reduction in 30-day mortality was observed (9% in the BNP group versus 17% in the control group; P = 0.039). CONCLUSIONS: Used in conjunction with other clinical information, rapid measurement of BNP in the emergency department improved the management of elderly patients presenting with acute dyspnoea and thereby reduced the time to discharge and the total treatment cost. In addition, BNP testing seemed to reduce 30-day mortality.

Acute Disease↗

Impact of diabetes mellitus on long-term outcome after unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy.

AIMS/HYPOTHESIS: We sought to evaluate the impact of diabetes mellitus on long-term outcome in patients with unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy. METHODS: We carried out a prospective cohort study in 270 diabetic and 1163 non-diabetic patients with unstable angina and non-ST-segment elevation myocardial infarction. All patients underwent coronary angiography and, if appropriate, subsequent revascularisation within 24 hours of admission. The primary endpoint was all-cause mortality during follow-up for up to 60 months. RESULTS: Diabetic patients had less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction. Percutaneous coronary intervention was performed in 53% of diabetic patients and 56% of non-diabetic patients. Coronary artery bypass grafting was done in 21% of diabetic patients and 12% of non-diabetic patients. In-hospital mortality (4.1% vs 1.3%; hazard ratio 3.47; 95% CI: 1.57 to 7.64; p=0.002) and long-term mortality (9.7% vs 4.9%; hazard ratio 2.11; 95% CI: 1.33 to 3.36; p=0.002) were significantly higher in diabetic patients. After adjustment for differences in baseline characteristics, diabetes mellitus was no longer an independent predictor of long-term mortality (hazard ratio 1.43; 95% CI: 0.74 to 2.78; p=0.292). CONCLUSIONS/INTERPRETATION: Diabetic patients treated with a very early invasive strategy for unstable angina and non-ST-segment elevation myocardial infarction have a higher in-hospital and long-term mortality that is largely explained by their less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction.

Aged↗

Renal function and long term mortality after unstable angina/non-ST segment elevation myocardial infarction treated very early and predominantly with percutaneous coronary intervention.

OBJECTIVES: To quantify the impact of baseline renal function on in-hospital and long term mortality in patients with unstable angina/non-ST elevation acute myocardial infarction (UA/NSTEMI) treated with a very early invasive strategy. DESIGN: Prospective cohort study of 1400 consecutive patients with UA/NSTEMI undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularisation strategy within 24 hours of admission. Patients were stratified according to calculated glomerular filtration rate (GFR) on admission. RESULTS: In-hospital mortality was 0% among patients with a GFR > or = 130 ml/min/1.73 m2, 0.4% with a GFR of 90-129 ml/min/1.73 m2, 2.6% with a GFR of 60-89 ml/min/1.73m2, and 5.1% with a GFR of < 60 ml/min/1.73 m2. Cumulative three year survival rates were 92.6%, 95.5%, 91.9%, and 76.8%, respectively. Patients with a GFR of < 60 ml/min/1.73 m2 were four times more likely to die in hospital (hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.8 to 9.1; p = 0.001) and four times more likely to die during long term follow up (HR 4.0, 95% CI 2.5 to 6.4; p < 0.001). After adjusting for potential confounders, a GFR of < 60 ml/min/1.73 m2 remained a strong independent predictor of long term mortality (HR 2.6, 95% CI 1.5 to 4.5; p = 0.001). CONCLUSIONS: Baseline renal function is a strong independent predictor of in-hospital and long term mortality after UA/NSTEMI treated with very early revascularisation.

Aged↗

Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study.

AIMS: To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). METHODS: Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. RESULTS: Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19). CONCLUSIONS: After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.

Adult↗

White blood cell count and long term mortality after non-ST elevation acute coronary syndrome treated with very early revascularisation.

OBJECTIVE: To evaluate the predictive value of white blood cell count (WBC) for short and long term mortality in patients with non-ST elevation acute coronary syndromes (NSTACS) treated with a very early invasive strategy. DESIGN: Prospective cohort study in 1391 consecutive patients with NSTACS undergoing very early revascularisation. Patients were stratified according to quartiles of WBC determined on admission. RESULTS: Kaplan-Meier survival analysis showed a cumulative three year survival of 93.8% in the first quartile of WBC (< 6800/mm(3)), 94.4% in the second quartile (6800-8000/mm(3)), 95.1% in the third quartile (8000-10000/mm(3)), and 82.4% in the fourth quartile (> 10000/mm(3)) at 36 months (p < 0.001 by log rank). Relative to patients in the three lower WBC quartiles, patients in the highest quartile were three times more likely to die during the hospitalisation (hazard ratio 3.2, 95% confidence interval (CI) 1.5 to 7.1; p = 0.003) and during long term follow up (hazard ratio 3.4, 95% CI 2.2 to 5.3; p < 0.001). By multivariate Cox regression analysis including baseline demographic, clinical, and angiographic covariables, WBC in the highest quartile remained a strong independent predictor of mortality (hazard ratio 3.3, 95% CI 1.9 to 5.6; p < 0.001). CONCLUSIONS: WBC is a strong independent predictor of short and long term mortality after NSTACS treated with very early revascularisation.

Cohort Studies↗

Regular follow-up after curative resection of nonsmall cell lung cancer: a real benefit for patients?

Even though complete resection is regarded as the only curative treatment for nonsmall cell lung cancer (NSCLC), >50% of resected patients die from a recurrence or a second primary tumour of the lung within 5 yrs. It remains unclear, whether follow-up in these patients is cost-effective and whether it can improve the outcome due to early detection of recurrent tumour. The benefit of regular follow-up in a consecutive series of 563 patients, who had undergone potentially curative resection for NSCLC at the University Hospital, was analysed. The follow-up consisted of clinical visits and chest radiography according to a standard protocol for up to 10 yrs. Survival rates were estimated using the Kaplan-Meier analysis method and the cost-effectiveness of the follow-up programme was assessed. A total of 23 patients (6.4% of the group with lobectomy) underwent further operation with curative intent for a second pulmonary malignancy. The regular follow-up over a 10-yr period provided the chance for a second curative treatment to 3.8% of all patients. The calculated costs per life-yr gained were 90,000 Swiss Francs. The cost-effectiveness of the follow-up protocol was far above those of comparable large-scale surveillance programmes. Based on these data, the intensity and duration of the follow-up was reduced.

Adult↗

Talcage by medical thoracoscopy for primary spontaneous pneumothorax is more cost-effective than drainage: a randomised study.

Simple thoracoscopic talcage (TT) is a safe and effective treatment of primary spontaneous pneumothorax (PSP). However, its efficacy has not previously been estimated in comparison with standard conservative therapy (pleural drainage (PD)). In this prospective randomised comparison of two well-established procedures of treating PSP requiring at least a chest tube, cost-effectiveness, safety and pain control was evaluated in 108 patients with PSP (61 TT and 47 PD). Patients in both groups had comparable clinical characteristics. Drainage and hospitalisation duration were similar in TT and PD patients. There were no complications in either group. The immediate success rate was different: after prolonged drainage (>7 days), 10 out of 47 PD patients, but only 1 out of 61 TT patients required a TT as a second procedure. Total costs of hospitalisation including any treatment procedure were not significantly different between TT and PD patients. Pain, measured daily by visual analogue scales, was statistically higher during the first 3 days in TT patients but not in those patients receiving opiates. One month after leaving hospital, there was no significant difference in residual pain or full working ability: 20 out of 58 (34%) versus 10 out of 47 (21%) and 36 out of 61 (59%) versus 26 out of 39 (67%) in TT versus PD groups, respectively. After 5 yrs of follow-up, there had been only three out of 59 (5%) recurrences of pneumothorax after TT, but 16 out of 47 (34%) after conservative treatment by PD. Cost calculation favoured TT pleurodesis especially with regard to recurrences. In conclusion, thoracoscopic talc pleurodesis under local anaesthesia is superior to conservative treatment by chest tube drainage in cases of primary spontaneous pneumothorax that fail simple aspiration, provided there is efficient control of pain by opioids.

Adolescent↗

Distinct endobronchial expression of matrix-metalloproteinases (MMP) and their endogenous inhibitors in lung cancer.

BACKGROUND: Degradation of extracellular matrix (ECM) and basement membranes is required for tumour cell invasion and metastasis. The ECM is degraded by matrix metalloproteinases (MMP) which are counteracted by tissue inhibitors of metalloproteinases (TIMP). In aggressive tumours the balance of proteolysis and antiproteolysis is disrupted, resulting in fast tumour progression and invasiveness. We examined MMP and TIMP expression patterns in bronchial washings of 58 consecutive lung tumour patients and 10 controls. Pathohistological investigations revealed squamous cell carcinoma (n = 23), adenocarcinoma (n = 18), small cell lung carcinoma (n = 9), and pulmonary metastases of extrapulmonary tumours (n = 8). MMP/TIMP expression was correlated to histology, location, or staging of tumours. METHODS: Expression and activity of MMP was identified by zymography and Western blotting. Expression of TIMP-1 and TIMP-2 was analysed by Western blotting and enzyme-linked immunosorbent assays. RESULTS: We identified MMP-1, MMP-2 and MMP-9, but not MMP-3 or MMP-8 in bronchial washings. All MMPs were expressed in the tumour-affected and the tumour-free parts of the lung. While MMP-1 and MMP-9 were present in all samples, the inactive precursor of MMP-2 was specifically expressed in adenocarcinoma or lung metastases of extrapulmonary tumours. No MMP-2 was found in controls. While TIMP-1 was expressed in all samples, TIMP-2 was not detectable. CONCLUSION: The tumour type-specific expression of the MMP-2 precursor in adenocarcinoma and lung metastases suggests that MMP-2 in the absence of TIMP-2 correlates with aggressive tumour progression and may serve as an indicator for poor prognosis.

Adenocarcinoma↗

Adenovirus-mediated wild-type p53 gene transfer in patients receiving chemotherapy for advanced non-small-cell lung cancer: results of a multicenter phase II study.

PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in patients undergoing first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable NSCLC were enrolled in an open-label, multicenter phase II study of three cycles of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175 mg/m(2), day 1), or regimen B, cisplatin (100 mg/m(2), day 1) plus vinorelbine (25 mg/m(2), days 1, 8, 15, and 22) in combination with intratumoral injection of 7.5 x 10(12) particles of SCH 58500 (rAd/p53, day 1). Responses of individual tumor lesions were assessed after each cycle, and gene transfer was examined in posttreatment tumor biopsies using reverse transcriptase polymerase chain reaction. RESULTS: There was no difference between the response rate of lesions treated with p53 gene therapy in addition to chemotherapy (52% objective responses) and lesions treated with chemotherapy alone (48% objective responses). Subgroup analysis according to the chemotherapy regimens revealed evidence for increased mean local tumor regressions in response to additional p53 gene therapy in patients receiving regimen B, but not in patients receiving regimen A. There was no survival difference between the two chemotherapy regimens, and the median survival of the cohort was 10.5 months (1-year survival, 44%). Transgene expression was confirmed in tumor samples from 68% of patients, and toxicities attributable to gene therapy were mild to moderate. CONCLUSION: Intratumoral adenoviral p53 gene therapy appears to provide no additional benefit in patients receiving an effective first-line chemotherapy for advanced NSCLC.

Adenoviridae↗

Severe bronchiolitis in acute Mycoplasma pneumoniae infection.

We report on a 17-year-old patient with severe bronchiolitis due to Mycoplasma pneumoniae infection. Despite an early 10-day course of clarithromycin, she developed progressive dyspnea, cough, fever, and severe obstructive ventilatory impairment. Sixteen days after onset of the disease a severe hemolytic anemia developed with only cold agglutinins positive at serologic screening. Thoracoscopic lung biopsy revealed diffuse bronchiolitis with suppurative intrabronchiolar inflammation, lymphohistiocytic "cuffing" of the bronchioli, and foam cell aggregates within neighboring alveoli. The infiltrate consisted mainly of CD3+, CD8+ lymphocytes and CD68+ macrophages. The diagnosis of Mycoplasma pneumoniae bronchiolitis was based on repeated complement fixation tests, which turned strongly positive only at day 74 after onset of the disease. Pulmonary function improved slowly under long-term prednisone treatment.

Acute Disease↗

Molecular mechanisms of TGF-(beta) antagonism by interferon (gamma) and cyclosporine A in lung fibroblasts.

Lung fibrosis is a fatal condition of excess extracellular matrix (ECM) deposition associated with increased transforming growth factor beta (TGF-beta) activity. Although much is known about its pathological features, our understanding of the signal transduction pathways resulting in increased ECM and collagen deposition in response to TGF-beta is still incompletely defined. We have previously reported that a JunD homodimer of the transcription factor AP-1 is specifically activated by TGF-beta in lung fibroblasts. Here we demonstrate that JunD is also specifically required for TGF-beta-induced effects. Antisense against JunD, but not c-fos or c-jun, significantly inhibited collagen deposition in response to TGF-beta in primary human lung fibroblasts. We then investigated the ability of pharmacological agents to inhibit TGF-beta-induced signaling and collagen deposition. Cs-A and IFN-gamma, but not glucocorticoids, cyclophosphamide, or azathioprine, inhibited TGF-beta-induced signaling, as assessed by luciferase reporter gene assays, and collagen deposition. TGF-beta antagonism by Cs-A was associated with direct inhibition of JunD activation, as demonstrated by electrophoretic mobility shift analyses. In contrast, the effects of IFN-gamma required signal transducer and activator of transcription (STAT)-1. We thus identify the JunD isoform of AP-1 as an essential mediator of TGF-beta-induced effects in lung fibroblasts. TGF-beta-induced signaling and collagen deposition are efficiently antagonized by Cs-A and IFN-gamma treatment, both of which exhibit distinct molecular mechanisms of action. These observations therefore offer novel targets for future therapy of fibrotic lung disease.

Cells, Cultured↗