Complication Of Idiopathic Pulmonary Fibrosis Research Articles

Association between high levels of nitrogen dioxide and increased cumulative incidence of lung cancer in patients with idiopathic pulmonary fibrosis.

Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. However, the association between individual exposure to air pollutants and lung cancer development in patients with IPF is unknown. This study aimed to assess the effect of individual exposure to nitrogen dioxide (NO2) on lung cancer development in patients with IPF. We enrolled 1085 patients from an IPF cohort in the Republic of Korea (mean age 65.6 years, males 80.6%). We estimated individual-level long-term exposures to NO2 at the patients' residential addresses using a national-scale exposure prediction model based on data from air quality regulatory monitoring stations. To evaluate the association between NO2 levels and lung cancer development in IPF, we used an individual- and area-level covariates adjusted model as our primary model. The estimated average annual NO2 concentration was 23.1 ppb. During a median follow-up of 4.3 years, 86 patients (7.9%) developed lung cancer. NO2 concentration was associated with lung cancer development in an unadjusted model (HR 1.219; p=0.042), while a marginal association was found in the primary model (HR 1.280; p=0.084). When NO2 concentration was stratified by the median value (21.0 ppb), exposure to high NO2 levels (≥21.0 ppb) was associated with a 2.0-fold increase in the risk of lung cancer development (HR 2.023; p=0.047) in the primary model. Individual exposure to high NO2 levels may increase the risk of lung cancer development in patients with IPF.

Latent inter-organ mechanism of idiopathic pulmonary fibrosis unveiled by a generative computational approach

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by complex lung pathogenesis affecting approximately three million people worldwide. While the molecular and cellular details of the IPF mechanism is emerging, our current understanding is centered around the lung itself. On the other hand, many human diseases are the products of complex multi-organ interactions. Hence, we postulate that a dysfunctional crosstalk of the lung with other organs plays a causative role in the onset, progression and/or complications of IPF. In this study, we employed a generative computational approach to identify such inter-organ mechanism of IPF. This approach found unexpected molecular relatedness of IPF to neoplasm, diabetes, Alzheimer’s disease, obesity, atherosclerosis, and arteriosclerosis. Furthermore, as a potential mechanism underlying this relatedness, we uncovered a putative molecular crosstalk system across the lung and the liver. In this inter-organ system, a secreted protein, kininogen 1, from hepatocytes in the liver interacts with its receptor, bradykinin receptor B1 in the lung. This ligand–receptor interaction across the liver and the lung leads to the activation of calmodulin pathways in the lung, leading to the activation of interleukin 6 and phosphoenolpyruvate carboxykinase 1 pathway across these organs. Importantly, we retrospectively identified several pre-clinical and clinical evidence supporting this inter-organ mechanism of IPF. In conclusion, such feedforward and feedback loop system across the lung and the liver provides a unique opportunity for the development of the treatment and/or diagnosis of IPF. Furthermore, the result illustrates a generative computational framework for machine-mediated synthesis of mechanisms that facilitates and complements the traditional experimental approaches in biomedical sciences.

Skeletal muscle atrophy and short-term mortality in patients with acute exacerbation of idiopathic pulmonary fibrosis: an observational cohort study

BackgroundSkeletal muscle atrophy, a common complication of idiopathic pulmonary fibrosis (IPF), and its presence upon diagnosis can indicate a poor prognosis. Patients with IPF frequently experience acute exacerbations (AE), which is associated with a high mortality rate. However, the association between skeletal muscle atrophy and short-term mortality remains unknown. MethodsWe performed a retrospective, multicenter cohort study of patients admitted for AE-IPF in Japan. The cross-sectional areas of the erector spinae muscle (ESMCSA) and the pectoralis muscle (PMCSA) were analyzed via single-slice computed tomography (CT). The primary outcome was 90-day mortality. Survival probability was estimated using the Kaplan–Meier method, and the log-rank test was used between the low and high groups of ESMCSA and PMCSA. We used multivariable Cox proportional-hazards models to evaluate the association between ESMCSA and PMCSA and prognosis. ResultsOf the 212 patients included, 94 (44%) died during the observation period. The low ESMCSA group (<25.6 cm2) had a significantly worse prognosis than that of the high ESMCSA group (≥25.6 cm2) (hazard ratio (HR) [95% confidence interval (CI)]: 1.52 [1.00–2.33], P = 0.049). Multivariable analyses showed that all-cause mortality was associated with low ESMCSA (model 1, adjusted HR [95% CI]: 1.59 [0.98–2.60]; model 2, 1.55 [0.95–2.56], and model 3, 1.67 [1.00–2.78], respectively). The adjusted HR of low PMCSA (<20.4 cm2) vs. high PMCSA (≥20.4 cm2) was 1.39 (95% CI: 0.88–2.20). ConclusionsLow ESMCSA on CT images is associated with a high 90-day mortality rate in patients with AE-IPF.

High complement protein C1q levels in pulmonary fibrosis and non-small cell lung cancer associated with poor prognosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common type of interstitial pneumonia. Lung cancer, mainly non-small cell lung cancer (NSCLC), is a complication of idiopathic pulmonary fibrosis. IPF is also an independent risk factor of lung cancer. Some studies have shown that the complement system can promote the progression of interstitial pulmonary fibrosis. In addition, C1q has also demonstrated to exert a tumor-promoting effect in many tumors. However, the role of C1q in idiopathic pulmonary fibrosis and lung cancer still remain unclear.MethodsWe selected common differentially expressed genes in IPF and non-small cell lung cancer using datasets from GEO, and investigated common hub gene. The hub genes were validated in IPF by establishing mouse model of IPF and using another four datasets from the GEO. Multiple databases were analyzed including those of Kaplan–Meier Plotter, Tumor Immune Estimation Resource (TIMER2.0) and the Human Protein Atlas (HPA) for NSCLC.ResultsIn this study, 37 common DEGs were identified in IPF and NSCLC including 32 up-regulated genes and 5 down-regulated genes, and C1q was identified as common hub gene. The methylation status of C1q decreased and the expression levels of C1q increased in both lung cancer and idiopathic pulmonary fibrosis. The prognosis of non-small cell lung cancer and IPF patients with high levels of C1q is poor.ConclusionsThese results show that C1q participates in pulmonary fibrosis and non-small cell lung cancer, and may be a potential diagnostic / prognostic biomarker or a therapeutic target.

Beta Adrenoceptor Ligands for the Treatment of Group 3 Pulmonary Hypertension and Cor Pulmonale: A Novel Therapeutic Target?

Pulmonary hypertension is a common complication of idiopathic pulmonary fibrosis (IPF), which leads to cor pulmonale and right-heart failure. β-blockers have been used extensively for the treatment of left heart disease, yet their use for right-heart failure is controversial. Recent studies have shown that β-blockers may be beneficial for the treatment of pulmonary arterial hypertension. However, whether β-receptors ligands are effective in PH and cor pulmonale associated with lung fibrosis has not been evaluated. Here we tested the effects of β adrenergic receptors (βAR) ligands in an experimental model of lung fibrosis and PH where fibrotic injury and cardiovascular complications co-exist. Using lung tissues isolated from explanted lungs from patients with IPF (with and without a diagnosis of PH), we determined βAR gene expression levels. Next, the capacity of either carvedilol (a βAR blocker) or clenbuterol (a β2AR agonist) to improve bleomycin (BLM)-induced alterations in cardiovascular physiology or lung function were assessed. These experiments were performed using lung function and transthoracic Echocardiography (Fig 1). After completion of these physiological readouts, the lungs were excised for assessment of fibrotic injury by RT-PCR, immunoblots and histology. Our experiments demonstrate reduced expression levels of the β2AR, but not β1AR or β3AR in IPF lung vs controls. We also report a significant correlation between elevated mPAP and reduced β2AR expression. Remarkably, our results using carvedilol or clenbuterol revealed that these agents improved right-heart function without impacting lung function. Taken together, these results demonstrate that β-receptor ligands are able to treat PH and cor pulmonale associated with lung fibrosis without altering fibrotic matrix deposition. These results are significant since PH is the single most significant predictor of mortality in IPF where limited therapies exist.

Treatment of complications and nonpharmacological management of idiopathic pulmonary fibrosis

Komplikationen der idiopathischen pulmonalen Fibrose (IPF) sind für einen relevanten Mortalitätsanteil verantwortlich. Als wichtigstes Beispiel ist diesbezüglich die akute Exazerbation anzuführen, deren Krankenhausletalität über 50 % beträgt bei einem mittleren Überleben von nur wenigen Monaten. Somit kommt der Betrachtung von Komplikationen eine große Bedeutung für Krankheitsverständnis sowie Therapieplanung zu. Des Weiteren ist in den letzten Jahren die Evidenz für pneumologische Rehabilitation bei IPF deutlich gestiegen und wird von der Amerikanischen und Europäischen Gesellschaft für Pneumologie (American Thoracic Society [ATS]/European Respiratory Society [ERS]) zur Verbesserung der körperlichen Leistungsfähigkeit, Lebensqualität und der Symptome empfohlen.

Acute exacerbations of fibrotic interstitial lung diseases.

Acute exacerbation (AE) is a severe complication of idiopathic pulmonary fibrosis (AE-IPF). In 2016, an international working group revised its definition and diagnostic criteria; however, few studies have assessed the frequency and prognosis of AE in patients with other fibrotic interstitial lung diseases (FILD). We used data from 1019 consecutive interstitial lung disease (ILD) patients initially evaluated between January 2008 and July 2015. All subject diagnoses were made by multidisciplinary discussion in December 2018. ILD was categorized as IPF (n = 462) and other FILD which included non-specific interstitial pneumonia (n = 22), chronic hypersensitivity pneumonitis (n = 29), connective tissue disease-associated ILD (n = 205) and unclassifiable ILD (n = 209). Using the 2016 definition of AE-IPF, we identified all subjects with an AE. During the observational period, 193 patients experienced a first AE (AE-FILD n = 69, AE-IPF n = 124). The time to first AE was significantly longer in FILD than IPF (log-rank test, P < 0.001). After adjusting for potentially influential confounders, FILD remained a significant predictor of longer time to first AE compared with IPF (hazard ratio: 0.453; 95% CI: 0.317-0.647, P = 0.006). In a multivariate Cox proportional analysis, baseline disease severity was closely associated with the incidence of AE-ILD. Even after adjustment for other clinical variables, AE had a negative impact on overall survival. AE-FILD and AE-IPF showed similar poor short-term outcomes. All forms of ILD are at risk of AE and have a similar outcome to AE-IPF.

Highlights of high-resolution computed tomography imaging in evaluation of complications and co-morbidities in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) represents a condition included in the heterogeneous group of interstitial lung diseases without known causes. The recent ATS/ERS/JRS/ALAT guidelines and the white paper published by the Fleischner Society have well-defined diagnosis and management of idiopathic pulmonary fibrosis. Idiopathic pulmonary fibrosis management is complex because it is also influenced by several co-morbidities and complications. The new frontier in idiopathic pulmonary fibrosis is represented by the effort to understand the complex mechanism of the pathogenesis and progression of disease in order to predict several consequences and co-morbidities. In our review, we tried to distinguish co-morbidities from complications of idiopathic pulmonary fibrosis. In each complication, we have reviewed the existing literature and we have emphasized the complex pathobiological pathway which links the progression of idiopathic pulmonary fibrosis to the development of the complication itself. For every co-morbidity, we tried to identify share common risk factors which explain the coexistence of idiopathic pulmonary fibrosis with its co-morbidities. We then analyzed high-resolution computed tomography (CT) aspects of co-morbidities and complications of idiopathic pulmonary fibrosis that the radiologist should be aware of. In this review, we focused on the role of high-resolution CT imaging in the evaluation of co-morbidities and complications in idiopathic pulmonary fibrosis because their early diagnosis and treatment could change the prognosis in patients with idiopathic pulmonary fibrosis. We have also pointed out that in some cases the final combined quantitative CT tools and conventional visual CT score would allow to get an accurate analysis and quantification of disease progression, co-morbidities, and complications of idiopathic pulmonary fibrosis in order to improve staging systems in idiopathic pulmonary fibrosis.

Macrophage Migration Inhibitory Factor (MIF) Inhibition in a Murine Model of Bleomycin-Induced Pulmonary Fibrosis.

Background: Pulmonary hypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that significantly contributes to morbidity and mortality. Macrophage migration inhibitory factor (MIF) is a critical factor in vascular remodeling of the pulmonary circulation. Objectives: We tested the effects of two small molecules targeting MIF on bleomycin (BLM)-induced collagen deposition, PH, and vascular remodeling in mouse lungs. Methods: We examined the distribution pattern of MIF, CD74, and CXCR4 in the lungs of patients with IPF-PH and the lungs of BLM-injected mice. Then, treatments were realized with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and N-(3-hydroxy-4-fluorobenzyl)-5 trifluoromethylbenzoxazol-2-thione 31 (20 mg/kg/day per os for 3 weeks) started 24 h after an intratracheal BLM administration. Results: More intense immunoreactivity was noted for MIF, CD74, and CXCR4 in lungs from IPF-PH patients and BLM-injected mice. Furthermore, we found that treatments of BLM-injected mice with ISO-1 or compound 31 attenuated lung collagen deposition and right ventricular systolic pressure increase. Additionally, reduced pulmonary inflammatory infiltration and pulmonary arterial muscularization were observed in the lungs of BLM-injected mice treated with ISO-1 or compound 31. Conclusions: Treatments with ISO-1 or compound 31 attenuates BLM-induced inflammation and fibrosis in lung, and prevents PH development in mice, suggesting that MIF is an important factor for IPF-PH development.

The Management of Patients With Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF), the most common form of fibrosing idiopathic interstitial pneumonia, is an inexorably progressive disease with a 5-year survival of ~20%. In the last decade, our understanding of disease pathobiology has increased significantly and this has inevitably impacted on the approach to treatment. Indeed, the paradigm shift from a chronic inflammatory disorder to a primarily fibrotic one coupled with a more precise disease definition and redefined diagnostic criteria have resulted in a massive increase in the number of clinical trials evaluating novel candidate drugs. Most of these trials, however, have been negative, probably because of the multitude and redundancy of cell types, growth factors and profibrotic pathways involved in disease pathogenesis. As a consequence, until recently IPF has lacked effective therapies. Finally, in 2014, two large phase 3 clinical trials have provided robust evidence that pirfenidone, a compound with anti-fibrotic, anti-oxidant and anti-inflammatory properties, and nintedanib, a tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor receptors are able to slow down functional decline and disease progression with an acceptable safety profile. While this is a major achievement, neither pirfenidone nor nintedanib cures IPF and most patients continue to experience disease progression and/or exacerbation despite treatment. Therefore, in recent years increasingly more attention has been paid to preservation of quality of life and, in the advanced phase of the disease, palliation of symptoms. Lung transplantation, the only curative treatment, remains a viable option for only a minority of highly selected patients. The unmet medical need in IPF remains high, and more efficacious and better tolerated drugs are urgently needed. However, a truly effective therapeutic approach should also address quality of life and highly prevalent concomitant conditions and complications of IPF.

Pulmonary artery size as a predictor of outcomes in idiopathic pulmonary fibrosis

Pulmonary hypertension (PH) is a well-recognised complication of idiopathic pulmonary fibrosis (IPF) and is predictive of a worse outcome. The prevalence of PH in the setting of IPF has not been well described in the literature, but has ranged from 32% to 85%.

Non-invasive screening for pulmonary hypertension in idiopathic pulmonary fibrosis

BackgroundPulmonary hypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that is associated with poor prognosis. Noninvasive screening for PH in IPF patients is challenging and a combination of several noninvasive determinations can improve discrimination. MethodsWe included 235 IPF patients who underwent right heart catheterization (RHC) as part of the lung transplant evaluation. We measured electrocardiographic (ECG) and echocardiographic variables as well as the pulmonary artery (PA) and ascending aorta (AA) diameters on chest CT. We recorded results of arterial blood gases (ABG), pulmonary function (PFT) and 6-min walk tests (6MWT). ResultsSeveral variables were predictors of PH in IPF patients in univariable models including a lower arterial oxygenation and 6MWT distance; worse right ventricular (RV) function, rightward deviation of the QRS axis and a higher FVC/DLCOc ratio, PA/AA diameter ratio, and estimated RV systolic pressure. In multivariable analysis, a worse RV function and higher PA/AA ratio remained predictors of PH (c-index 0.75 (0.65–0.84)). Similarly, a worse RV function, a higher PA/AA ratio and a rightward QRS axis deviation were independent predictors of precapillary PH (c-index 0.86 (0.76–0.92)). A combination of PA/AA diameter ratio <1.1, a QRS axis <90° and normal RV function showed a negative predictive value of 85% for precapillary PH. ConclusionsThere are significant differences in ECG, echocardiographic, chest CT, PFT and ABG parameters between IPF patients with and without PH. However, these noninvasive tests alone or combination have limited discrimination ability for PH screening in IPF.

Abstract 12336: Non-invasive Screening for Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

Introduction: Pulmonaryhypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that is associated with poor prognosis. Screening for PH in IPF patients proves to be challenging. Hypothesis: We hypothesized that combining several non-invasive studies can predict the presence of PH in IPF patients. Methods: We included 235 IPF patients who underwent right heart catheterization (RHC) as part of the lung transplant evaluation. We measured ECG and echocardiographic variables as well as the pulmonary artery (PA) diameter and ascending aorta (AA) diameters on chest CT. We recorded results of arterial blood gases (ABG), pulmonary function (PFT) and 6-min walk tests (6MWT). Results: Several variables were predictors of PH in IPF patients in univariate models including arterial oxygenation, 6MWT distance, worse right ventricular (RV) function, the QRS axis, FVC/DLCOc ratio, PA/AA diameter ratio and estimated RV systolic pressure. In multivariate analysis, RV function and PA/AA ratio remained predictors of PH (c-statistics 0.75 (0.65-0.84), accuracy 71.4%). Similarly, RV function, PA/AA ratio and QRS axis were independent predictors of precapillary PH (c-statistics 0.86 (0.76-0.92), accuracy 84.2%). A combination of PA/AA diameter ratio &lt;1.1, a QRS axis &lt;90° and normal RV function showed a negative predictive value of 85% for precapillary PH. Conclusions: There are significant differences in ECG, echocardiographic, chest CT, PFT and ABG parameters between IPF patients with and without PH. However, these noninvasive tests alone or combination are not accurate enough for PH screening in IPF.

Factors predicting pulmonary hypertension in idiopathic pulmonary fibrosis patients

Abstract Context Pulmonary hypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) and an important pathophysiologic mechanism of exercise intolerance and poor quality of life in these patients. Aims The aims of this study were to assess predictors of PH in IPF from both resting pulmonary function test (PFT) and cardiopulmonary exercise testing (CPET) parameters and to establish cut-off values from resting PFT and CPET parameters for the prediction of PH. Settings and design This was a randomized, double-blind, and prospective study. Patients and methods Thirty-five patients with stable IPF were assessed in terms of resting pulmonary functions, arterial blood gases (ABG), echocardiography, and incremental CPET. Patients were classified into a PH group and a non-pulmonary-hypertension group. Statistical analysis Both groups were compared in terms of resting PFT and CPET parameters. A receiver operating characteristic curve was constructed to establish cut-off values for the prediction of PH. Results PH was observed in 13 (37.14%) patients. There were no significant differences between both groups in age and sex. forced vital capacity (FVC)%, forced expiratory volume in one second (FEV1)%, inspiratory capacity, resting and exercise partial arterial oxygen tension (PaO2) and arterial oxygen saturation (SaO2), and oxygen consumption (VO2%) were significantly reduced in the PH group, whereas the dyspnea score, resting and exercise PaCO2, respiratory frequency, and minute ventilation were significantly increased in the PH group. The receiver operating characteristic curve showed that resting SaO2 of 92.9% or less and exercise SaO2 of 87% or less had sensitivity of 84.6, and 100%, and specificity of 90.9 and 81.8%, respectively. Conclusion Marked deterioration in resting PFT, exercise parameters, and SaO2 can predict PH in IPF patients.

Adding Insult to Injury: Complications of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a distinctive form of chronic interstitial lung disease occurring primarily in older adults, more often male [Raghu G et al. Am J Respir Crit Care Med 2011]. The estimated prevalence of IPF is 14 to 43 per 100,000 and an estimated incidence is 7 to 16 per 100,000, depending on how it is defined [Raghu G et al. Am J Respir Crit Care Med 2006]. Prognosis can be predicted by the radiographic extent of the disease, amount of fibrosis, presence of pulmonary hypertension, and comorbidities (emphysema, lung cancer, and coronary artery disease).

Herpes Virus Infection Is Associated with Vascular Remodeling and Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

BackgroundPulmonary hypertension (PH) represents an important complication of idiopathic pulmonary fibrosis (IPF) with a negative impact on patient survival. Herpes viruses are thought to play an etiological role in the development and/or progression of IPF. The influence of viruses on PH associated with IPF is unknown. We aimed to investigate the influence of viruses in IPF patients focusing on aspects related to PH. A laboratory mouse model of gamma-herpesvirus (MHV-68) induced pulmonary fibrosis was also assessed.MethodsLung tissue samples from 55 IPF patients and 41 controls were studied by molecular analysis to detect various viral genomes. Viral molecular data obtained were correlated with mean pulmonary arterial pressure (mPAP) and arterial remodelling. Different clinical and morphological variables were studied by univariate and multivariate analyses at time of transplant and in the early post-transplant period. The same lung tissue analyses were performed in MHV-68 infected mice.ResultsA higher frequency of virus positive cases was found in IPF patients than in controls (p = 0.0003) and only herpes virus genomes were detected. Viral cases showed higher mPAP (p = 0.01), poorer performance in the six minute walking test (6MWT; p = 0.002) and higher frequency of primary graft (PGD) dysfunction after lung transplant (p = 0.02). Increased arterial thickening, particularly of the intimal layer (p = 0.002 and p = 0.004) and higher TGF-β expression (p = 0.002) were demonstrated in viral cases. The remodelled vessels showed increased vessel cell proliferation (Ki-67 positive cells) in the proximity to metaplastic epithelial cells and macrophages. Viral infection was associated with higher mPAP (p = 0.03), poorer performance in the 6MWT (p = 0.008) and PGD (p = 0.02) after adjusting for other covariates/intermediate factors. In MHV-68 infected mice, morphological features were similar to those of patients.ConclusionHerpesviral infections may contribute to the development of PH in IPF patients.

A Tribute to Peter M. Lynagh 1935–2011

Peter M. Lynagh passed away on October 9, 2011, from complications of Idiopathic Pulmonary Fibrosis. To me, Peter was not only a long-time colleague but also a scholar, professor, mentor and friend. He was one of the first people to greet and welcome me when I joined the University of Maryland faculty in the Fall of 1970. He eased my transition from doctoral student to young faculty member by serving as a caring mentor and loyal friend. This friendship extended to our immediate families as Peter was also a devoted godfather to my youngest daughter.Throughout the years we carried out a number of successful research projects together. Peter was especially proud of his involvement in some of the earliest academic research relating to the role of women and minorities in transportation and logistics.“Dr. L.” as he was affectionately known by his students and colleagues was a member of the marketing faculty at the University of Baltimore since 1982 and was one of the Merrick School of Business' most dedicated and decorated teachers. He was the recipient of the Frank Baker Teaching Professorship from 2006–9 and was awarded the Dean James Chair for Distinguished Teaching in 2010.Peter was a proud and active member of AST&L; he was a member of the AST&L Board of Examiners from 1990–98 and chaired the Board in 1997–98. Likewise he was a book review editor for the Transportation Journal since the Fall 2006 issue. He also was an active member of the American Marketing Association and the Association of Transportation Practitioners.Peter had a passion for living and this was reflected in his love of a variety of sports. He enjoyed playing golf and softball and was an avid fan of Baltimore Orioles baseball and Washington Redskins football. He also shared with this writer an interest in horse racing and was known to make several visits a year to Pimlico Racetrack in Baltimore for some wagering. We used to joke that this activity was just a natural extension of our interest in logistics as it represented yet another “mode” or form of transportation!The academic and business communities as well as society at large are far better as a result of the involvement and accomplishments of “Dr. L.” His life was a testament to his love of teaching, the power of humility, compassion for others, and the true meaning of loyalty and integrity.The Lynagh Memorial Fund has been established to honor Peter's contributions and accomplishments. Checks made payable to the UB Foundation-Lynagh Memorial, can be mailed to the Office of Annual Giving, University of Baltimore, 1130 N. Charles Street, Baltimore, MD 21201.

Exacerbations of idiopathic pulmonary fibrosis treated with corticosteroids and cyclophosphamide pulses

To the Editors: Acute exacerbations (AEs) are now recognised as a frequent and severe complication of idiopathic pulmonary fibrosis (IPF). In a large series, 1- and 3-yr incidences were 14.2% and 20.7%, respectively [1]. New diagnostic criteria were published in 2007 [2]. The pathogenesis of these episodes remains unknown, although invasive procedures have been described as possible triggers. Prognosis is poor, with a short-term mortality rate of 45–85%. There is no consensus regarding treatment, as no published study has compared the efficiency of different treatment regimens, and treatment often differs between patients within a given study [1–4]. Since 2005, exacerbations of IPF identified in our referral centre (Centre Hospitalier Regional de Lille, Lille, France) have been treated with pulses of methylprednisolone followed by pulses of cyclophosphamide [5]. The main goal of the present retrospective study was to evaluate the mortality of exacerbations of IPF treated with this regimen. Following admission for aggravation of dyspnoea, a series of tests were run to determine diagnosis and functional impairment. When an exacerbation of IPF was diagnosed, patients were treated with a methylprednisolone pulse (1,000 mg) at days 1–3 and on day 4 placed on an escalating regimen of cyclophosphamide with an initial dose of 500 mg intravenously [5]. The dose of cyclophosphamide was increased by 200 mg every 2 weeks, provided the total white blood cell count remained at >3,000 cells·mm−3. The maximum single administered dose was 1,500 mg of cyclophosphamide. The diagnosis of IPF was reassessed for the purpose of this study …

Fibrotic Idiopathic Interstitial Pneumonia: High-Resolution Computed Tomography Considerations

The fibrotic idiopathic interstitial pneumonias comprise usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). The characteristic high-resolution computed tomography findings of UIP are reticular abnormality and honeycombing with basal and peripheral predominance. Honeycombing is the strongest predictor of UIP. The extent of fibrosis on computed tomography (CT) is an important prognostic indicator in idiopathic pulmonary fibrosis (IPF). When ground-glass attenuation is seen in IPF it commonly progresses to fibrosis and honeycombing. Imaging may help to detect complications of IPF, including accelerated progression, lung cancer, and secondary infection. Our understanding of the clinical and radiological features of NSIP is still evolving. The CT finding of extensive ground-glass abnormality and some reticular abnormality, with basal and peripheral predominance, is strongly suggestive of NSIP. However, the CT appearances of NSIP overlap with those of UIP, organizing pneumonia (OP), and desquamative interstitial pneumonia (DIP), and biopsy may be necessary to sort this out. Other idiopathic pneumonias that may be associated with CT evidence of lung fibrosis include DIP, OP, acute interstitial pneumonia, and lymphoid interstitial pneumonia.