Chronic Lung Changes Research Articles

Post-tuberculosis lung disease and chronic obstructive pulmonary disease.

The burden of chronic airway diseases, including chronic obstructive pulmonary disease (COPD), continues to increase, especially in low- and middle-income countries. Post-tuberculosis lung disease (PTLD) is characterized by chronic lung changes after the "cure" of pulmonary tuberculosis (TB), which may be associated with the pathogenesis of COPD. However, data on its prevalence, clinical manifestations, computed tomography features, patterns of lung function impairment, and influencing factors are limited. The pathogenic mechanisms underlying PTLD remain to be elucidated. This review summarizes the recent advances in PTLD and TB-associated COPD. Research is urgently needed both for the prevention and management of PTLD.

Radiological Follow-Up of Adults Hospitalised With Pneumonia and SARS-Cov-2 Infection, In Bristol UK, During The CO

Introduction: Radiological change which may be attributed to infection can also be attributable to lung cancer. Patients with SARS-CoV-2 infection can develop groundglass lung opacification which may result in chronic lung changes. Current British Thoracic Society (BTS) guidelines recommend patients with pneumonia and COVID19 undergo repeat chest radiography. Methods: A single-centre audit of patients hospitalised with communityacquired pneumonia or COVID19 over three time periods during the COVID19 pandemic (Aug-Dec 2020, Jun-Aug 2021, Dec-Jan 2022). We assessed whether patients were eligible for radiological follow-up and if repeat radiological investigation occurred. Results: 1040 adults were hospitalised with infective radiological change (pneumonia=596, COVID19=444). 831/1040 patients (80%) required radiological follow-up under BTS guideline criteria: there was minimal difference between the first two time periods studied. Patients hospitalised with CAP were less likely to have radiological follow-up planned than those admitted with COVID19 disease (49% versus 59% respectively). Following a change in hospital policy, follow-up rates increased to 69% and 71% for pneumonia and COVID19. Overall, only 47% eligible patients received follow-up in line with current guidelines. Conclusion: BTS guideline adherence is important to avoid delay in diagnosing underlying malignancy or chronic lung disease. Radiological follow-up following CAP and COVID19 may be suboptimal, with a paucity of data. Follow-up arranged under the hospital team was more likely to occur than when the GP was responsible for instigating repeat radiological imaging. Further investigation into rates of radiological follow-up should be undertaken, including reasons for non-adherence, to ensure patients receive appropriate treatment following respiratory infection

Factors Affecting the Risk of Interstitial Lung Disease Development in Hospitalized Patients With COVID-19 Pneumonia.

Coronavirus disease 2019 (COVID-19) related chronic lung changes secondary to severe disease have become well known. The aim of this study was to determine the risk factors that affect the development of interstitial lung disease in subjects with COVID-19 pneumonia who were hospitalized. Patients hospitalized with COVID-19 pneumonia between June 2020 and March 2021 were retrospectively analyzed. Smoking histories, comorbidities, reverse transcriptase polymerase chain reaction test results, laboratory parameters at the time of the diagnosis, oxygen support, the use of corticosteroids with dosage and duration data, the need for ICU care were recorded. High-resolution computed tomographies (HRCT) were obtained for study population in their 3-6 months follow-up visit. The subjects were classified as having residual parenchymal lung disease if a follow-up HRCT revealed parenchymal abnormalities except pure ground-glass opacities (the residual disease group). The control group consisted of the subjects with normal chest radiograph or HRCT in their follow-up visit or the presence of pure ground-glass opacities. Two groups were compared for their demographic and clinical abnormalities, laboratory parameters, treatment regimens, and the need for ICU care. The study included 446 subjects. The mean ± SD age was 58.4 ± 13.87 years, with 257 men (57.6%). Although 55 subjects had normal HRCT features on their follow-up HRCT, 157 had abnormal lung parenchymal findings. Univariate logistic regression analysis revealed statistically significant results for age, sex, corticosteroid treatment, and the need for ICU care for predicting interstitial lung disease development (P < .001, P = .003, P < .001, and P < .001, respectively). Also, the residual disease group had significantly higher leukocyte and neutrophil counts and lower lymphocyte counts (P < .001, P < .001, P = .004, respectively). Correlated with these findings, neutrophil-to-lymphocyte ratios and platelet-to-lymphocyte ratios were significantly higher in the residual disease group (P < .001 and P = .008, respectively). Residual parenchymal disease was observed 3-6 months after discharge in one third of the subjects hospitalized with COVID-19 pneumonia. It was observed that interstitial lung disease developed more frequently in older men and in those subjects with more-severe disease parameters.

Respiratory Infections in Patients with Primary Immunodeficiency

Recurrent and life-threatening respiratory infections are nearly universal in patients with primary immunodeficiency diseases (PIDD). Early recognition, aggressive treatment, and prophylaxis with antimicrobials and immunoglobulin replacement have been the mainstays of management and will be reviewed here with an emphasis on respiratory infections. Genetic discoveries have allowed direct translation of research to clinical practice, improving our understanding of clinical patterns of pathogen susceptibilities and guiding prophylaxis. The recent identification of inborn errors in type I interferon signaling as a basis for life-threatening viral infections in otherwise healthy individuals suggests another targetable pathway for treatment and/or prophylaxis. The future of PIDD diagnosis will certainly involve early genetic identification by newborn screening before onset of infections, with early treatment offering the potential of preventing disease complications such as chronic lung changes. Gene editing approaches offer tremendous therapeutic potential, with rapidly emerging delivery systems. Antiviral therapies are desperately needed, and specific cellular therapies show promise in patients requiring hematopoietic stem cell transplantation. The introduction of approved therapies for clinical use in PIDDislimited by the difficulty of studying outcomes in rarepatients/conditions with conventional clinical trials.

PNEUMONIA MASQUERADING AS ANTI-SYNTHETASE SYNDROME

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Anti-synthetase syndrome (ASS) is a rare autoimmune disorder, characterized by anti-aminoacyl transfer RNA synthetase antibodies along with clinical features that can include interstitial lung disease, myositis, Raynaud's phenomenon, non-erosive arthritis, unexplained fever, and/or mechanic's hands. [1] Most patients with ASS with lung involvement present with chronic lung changes, we are describing a case of atypical presentation of ASS lung disease with organizing pneumonia. CASE PRESENTATION: A 60-year-old woman with a history of obstructive sleep apnea, asthma/COPD, and hypothyroidism presented with progressive shortness of breath. The patient had two recent hospitalizations for asthma exacerbation and pneumonia. Chest CT showed patchy scattered ground-glass opacities and consolidative changes with mild traction bronchiectasis changes. Autoimmune workup was positive for anti-SSA (mildly) and ANA but negative for RF, anti-smith, RNP, SSB, SCL70, centromere, PR3, MPO, RNA-Pol 3, and CCP antibodies. Myositis panel was positive for PL-12 Ab. Lung biopsy was consistent with a predominant pattern of organizing pneumonia. In the absence of myositis, the patient was diagnosed with ASS. The patient was initiated on mycophenolic acid and prednisone therapy. Initial pulmonary function tests showed FEV1/FVC is 74, FEV1 is 1.33L (61% of predicted) and FVC is 1.79L (66% of predicted), following treatment repeat PFTs in 3 months showed FEV1/FVC is 68, FEV1 is 1.45L (65% of predicted) and FVC is 2.13L (76% of predicted). Her exercise capacity improved with a six-minute walk test showing a walk distance of 177m with 3 L oxygen before treatment which improved to 435 m with 1 L oxygen post-treatment after 3 months. DISCUSSION: ASS is a group of inflammatory myopathies that requires evidence of anti-aminoacyl transfer RNA synthetase autoantibody and one or more of the following: mechanic's hands, Raynaud's phenomenon, myositis, ILD, arthritis, and/or unexplained fever. [2] Most cases are either misdiagnosed as idiopathic ILD or inflammatory myopathy. CONCLUSIONS: We presented a case of ASS with biopsy-proven organizing pneumonia. Organizing pneumonia is a very rare presentation of ASS and should be kept in mind while evaluating patients with ASS. REFERENCE #1: 1. Stone KB, Oddis CV, Fertig N, Katsumata Y, Lucas M, Vogt M, Domsic R, Ascherman DP. Anti–Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis & Rheumatism. 2007; 56:3125–3131. [PubMed: 17763431] REFERENCE #2: 2. References Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: What progress has been made in the past 35 years? Chest. 2010; 138:1464–1474. [PubMed: 21138882] DISCLOSURES: No relevant relationships by Bharat Bhandari, source=Web Response No relevant relationships by Rahat Hussain, source=Web Response No relevant relationships by Soma Sundara Shravan Jyothula, source=Web Response

ACUTE PULMONARY EMBOLISM AND HEMOPTYSIS IN A PATIENT WITH CYSTIC FIBROSIS

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Cystic fibrosis (CF) is an autosomal recessive disease that occurs due to reduced functioning of an apical membrane protein, the CF transmembrane conductance regulator (CFTR), found on the surface of epithelial cells [1]. Lung disease in CF is characterized by obstruction of the airway and bronchiectasis (King et al). We present a unique case of an unprovoked acute on chronic pulmonary embolism (PE) in a patient with CF at our institution. CASE PRESENTATION: A 58 year old male patient with a history of CF on elexacaftor-tezacaftor-ivacaftor presented to the ED with one-day history of left-sided pleuritic chest pain. Additionally, the patient endorsed one episode of hemoptysis. Of note, the patient underwent a bronchial artery embolization 10 years ago for frequent episodes of hemoptysis. Computed tomography (CT) angiography of the chest was significant for filling defects consistent with the presence of bilateral pulmonary emboli. Echocardiogram was significant for mildly elevated pulmonary artery systolic pressure. Given the history of hemoptysis, the patient was started on an intravenous (IV) unfractionated heparin drip. A ventilation-perfusion (V/Q) scan was obtained to determine the chronicity of the pulmonary emboli. The V/Q scan demonstrated multiple perfusion defects, consistent with both acute and chronic pulmonary embolism. Further imaging and bloodwork were not suggestive of occult malignancy or hypercoagulable disorder. The patient was later transitioned to weight-based enoxaparin sodium with warfarin. DISCUSSION: Previous studies have focused predominantly on venous thromboembolism (VTE) events and hypercoagulability in children with CF. There is evidence which suggests that CF results in the development of a hypercoagulable state. This is thought to be a result of vitamin K deficiency or hepatic dysfunction, and consequently, lower levels of protein S and C [2]. Due to medical advancements in managing CF, there is an increasing need for studies and guidelines regarding lifetime VTE risk, as well as choice and duration of anticoagulation in adults with CF. The presence of hemoptysis, a common feature of CF, may further complicate management of VTE. Several mechanisms have been proposed for the association of hemoptysis with CF, including the development of dilated vessels in the bronchial circulation and the presence of bronchiectasis leading to vascular erosion [3]. In this case, the risk of recurrence of major bleeding was weighed against the need for prompt anticoagulation. CONCLUSIONS: Overlap of symptoms with CF lung disease, as well as chronic lung changes on imaging, may complicate diagnosis of acute on chronic PE in patients with CF. In addition, acute PE with concurrent hemoptysis presents a therapeutic challenge. REFERENCE #1: King, C. S., Brown, A. W., Aryal, S., Ahmad, K., & Donaldson, S. (2019). Critical care of the adult patient with cystic fibrosis. Chest, 155(1), 202-214. REFERENCE #2: Raffini, L. J., Raybagkar, D., Blumenstein, M. S., Rubenstein, R. C., & Manno, C. S. (2006). Cystic fibrosis as a risk factor for recurrent venous thrombosis at a pediatric tertiary care hospital. The Journal of pediatrics, 148(5), 659-664. REFERENCE #3: Efrati, O., Harash, O., Rivlin, J., Bibi, H., Meir, M. Z., Blau, H., ... & Modan-Moses, D. (2008). Hemoptysis in Israeli CF patients—prevalence, treatment, and clinical characteristics. Journal of Cystic Fibrosis, 7(4), 301-306. DISCLOSURES: No relevant relationships by Bahadur Ali, source=Web Response No relevant relationships by Taylor Charter, source=Web Response No relevant relationships by Winnie Chu, source=Web Response No relevant relationships by Nikolaos Hatzis, source=Web Response No relevant relationships by Anita Kim, source=Web Response No relevant relationships by Sora Lee, source=Web Response No relevant relationships by Samantha Shetty, source=Web Response

“CHYLO,” IS IT ME YOU'RE LOOKING FOR? A CASE OF TRANSUDATIVE CHYLOTHORAX

SESSION TITLE: Medical Student/Resident Disorders of the Pleura Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Chylothorax is an uncommon type of pleural effusion which is usually exudative in nature. Transudative chylothoraces are an exceedingly rare entity, about 40% of which can be attributed to liver cirrhosis. CASE PRESENTATION: A 69-year-old female with hypertension, IDDM, and NASH/liver cirrhosis, presented with 5 days of shortness of breath and increasing abdominal girth. Examination revealed an obese, ill-appearing female, with stable vital signs, tachypnea requiring 4 L nasal cannula, diminished breath sounds over RM and RL lobes with dullness to percussion, ascitic abdomen without tenderness, without jaundice or other stigmata of liver disease. Laboratory panel was significant for lactic acidosis of 5 mmol/L and hypoalbuminemia. Imaging revealed a large right-sided pleural effusion and moderate ascites. She received aggressive IV fluids, empiric antibiotics, and underwent diagnostic thoracentesis consistent with a transudative effusion. Pleural fluid revealed a “milky” substance; triglyceride level was therefore checked with a value over 200 mg/dL. Her gram stain and culture were negative. Cytology was unremarkable. Patient had no history of trauma or surgeries. CT imaging had no evidence of lymphadenopathy or chronic lung changes. Echocardiogram ruled out CHF and pericarditis. A rheumatic panel was negative. There was no eosinophilia to suggest a parasitic infection. Quantiferon was negative. Paracentesis could not be performed due to small volume of ascites. Chest tube was placed for symptom relief. Given drainage of over 1 L output per day, total parenteral nutrition (TPN), chyle leak diet, and octreotide were started. Chest tube was removed after 10 days given decreasing output. Repeat pleural analysis showed a triglyceride level of 17 mg/dL. TPN was stopped and she was transitioned to a regular diet. Her chylothorax was attributed to liver cirrhosis. She was started on diuretics and discharged home with close follow-up. DISCUSSION: Emphasis must be placed on reviewing all aspects of the pleural fluid analysis including color, with chylothorax on the differential. Transudative chylothorax formation likely occurs due to chylous ascites transmigration through the diaphragm, with cirrhotic portal hypertension causing increased pressure in the thoracic duct. Once trauma is eliminated, malignancy, CHF, SVC obstruction, infections, sarcoidosis, and rheumatologic causes should be ruled out. Treatment relies on decreasing thoracic duct volume and inhibiting intestinal chyle absorption via somatostatin analogues, thoracentesis, and diet. Diuretics and transjugular intrahepatic portosystemic shunting were further treatment options for our patient given her liver cirrhosis. CONCLUSIONS: As transudative chyloraces are rare, clinicians may fail to recognize cirrhosis on the differential and fail to treat the underlying cause. Reference #1: Bhardwaj, Himanshu, et al. “Transudative Chylothorax in a Patient with Liver Cirrhosis: A Rare Association.” Heart & Lung, vol. 44, no. 4, 1 May 2015, pp. 363–365., doi:10.1016/j.hrtlng.2015.03.008. Reference #2: Mukherjee, Arindam, et al. “Transudative Chylothorax: an Uncommon Illness Due to a Common Cause.” BMJ Case Reports, 19 Jan. 2018, doi:10.1136/bcr-2017-223158. Reference #3: Schild, Hans H., et al. “Treatment Options in Patients With Chylothorax.” Deutsches Aerzteblatt Online, vol. 110, no. 48, 2013, pp. 819–826., doi:10.3238/arztebl.2013.0819. DISCLOSURES: No relevant relationships by Robert Gallagher, source=Web Response No relevant relationships by Loren Inigo-Santiago, source=Web Response No relevant relationships by Polina Pinkhasova, source=Web Response

Clinical, Immunological, and Functional Characterization of Six Patients with Very High IgM Levels.

Very high IgM levels represent the hallmark of hyper IgM (HIGM) syndromes, a group of primary immunodeficiencies (PIDs) characterized by susceptibility to infections and malignancies. Other PIDs not fulfilling the diagnostic criteria for HIGM syndromes can also be characterized by high IgM levels and susceptibility to malignancies. The aim of this study is to characterize clinical phenotype, immune impairment, and pathogenic mechanism in six patients with very high IgM levels in whom classical HIGM syndromes were ruled out. The immunological analysis included extended B-cell immunophenotyping, evaluation of class switch recombination and somatic hypermutation, and next generation sequencing (NGS). Recurrent or severe infections and chronic lung changes at the diagnosis were reported in five out of six and two out of six patients, respectively. Five out of six patients showed signs of lymphoproliferation and four patients developed malignancies. Four patients showed impaired B-cell homeostasis. Class switch recombination was functional in vivo in all patients. NGS revealed, in one case, a pathogenic mutation in PIK3R1. In a second case, the ITPKB gene, implicated in B- and T-cell development, survival, and activity was identified as a potential candidate gene. Independent of the genetic basis, very high IgM levels represent a risk factor for the development of recurrent infections leading to chronic lung changes, lymphoproliferation, and high risk of malignancies.

WS20.3 Lung clearance index and Aspergillus colonization are clinical markers of chronic lung changes by spirometry controlled CT in children with cystic fibrosis

WS20.3 Lung clearance index and Aspergillus colonization are clinical markers of chronic lung changes by spirometry controlled CT in children with cystic fibrosis

Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration

Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model. Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure. Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis (p<0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group. We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration.

INTRAUTERINE GROWTH RESTRICTION AFFECTS INSULIN GROWTH FACTOR BINDING PROTEIN 3 BUT NOT INSULIN-LIKE GROWTH FACTOR 1 RECEPTOR EXPRESSION IN THE DEVELOPING RAT LUNG.

Background Intrauterine growth restriction (IUGR) predisposes neonates toward chronic lung changes characterized by mesenchymal thickening. Insulin-like growth factor 1 (IGF-1) plays a crucial role in normal lung growth and development. Key modulators of IGF-1 activity include IGFBP-3 and IGF-1r. Previous studies have shown that IGFBP-3 binds IGF-1 and decreases its activity. In addition, evidence suggests that IGFBP-3 may exhibit growth inhibitory effects independent of its ability to down-regulate IGF-1 activity. Specifically, IGFBP-3 has been shown to inhibit the growth of fibroblasts derived from IGF-1r knockout mice. IGF-1r is a tyrosine kinase receptor that mediates the effects of IGF-1. Objective We hypothesized that IUGR would decrease IGFBP-3 expression in the developing rat lung and thereby contribute to increased IGF-1 activity and mesenchymal thickening. Furthermore, we hypothesized that these changes would be independent of IGF-1r expression. Design/Methods To prove these hypotheses, we used a rat model of IUGR induced through uteroplacental insufficiency. Lungs of control and IUGR rats ( n = 6-8 litters per group) at day 0 and day 21 were harvested and flash frozen. We measured relative mRNA levels of IGFBP-3 and IGF-1r with RT-PCR at day 0 and day 21. We also measured IGFBP-3 protein levels in day 0 rats. Results Significant results are expressed as percent of control ± SEM. IGF-1r mRNA levels were not different between IUGR and control rat lungs at either day 0 ( p = .66) or day 21 ( p = .32). While IGFBP-3 mRNA and protein levels did not differ at day 0 ( p = .81 and .90, respectively), mRNA levels differed significantly by day 21 (40.1% ± 7.0%, p = .05). Conclusions We conclude that IUGR decreases IGFBP-3 mRNA levels in the postnatal rat lung. IGF-1r expression is unaffected by IUGR. These results are particularly intriguing because although IUGR leads to mesenchymal thickening in the day 21 rat lung, we have previously demonstrated that IGF-1 mRNA expression in the postnatal IUGR rat lung is unchanged. We speculate that decreased IGFBP-3 during alveolarization results in increased IGF-1 bioavailability, which contributes to the mesenchymal thickening seen in the postnatal IUGR rat lung. This may be secondary to IUGR-induced imprinting on the IGFBP-3 gene that subsequently decreases its expression. Supported by the CHRC.

Awareness of Wilson-Mikity Syndrome: A Rare Complication of Chorioamnionitis

Summary Objective Wilson-Mikity syndrome is a rare neonatal morbidity of chorioamnionitis. It is characterized by insidious onset of progressive respiratory distress and may eventually lead to diffusely emphysematous lung changes. We report a mother who suffered from chorioamnionitis and who delivered a premature infant with Wilson-Mikity syndrome that was confirmed after delivery. Case Report A 33-year-old woman received tocolytic therapy from 19 weeks of gestation. Preterm premature rupture of membranes occurred at 24 weeks of gestation. Amniotic fluid culture yielded pseudomonas infection at 26 weeks of gestation. Despite supplementary tocolytics and a third-generation cephalosporin, a premature female infant was delivered vaginally at 26 weeks of gestation. Deteriorating respiratory symptoms and early chronic lung changes on chest radiography were found from the early third week of life. Wilson-Mikity syndrome was diagnosed based on the clinical and radiologic manifestations. The baby's respiratory condition improved under combination therapy with antibiotics, a bronchodilator, a steroid, and a synthetic surfactant, but she was hospitalized because of feeding problems. Conclusion The obstetrician must be aware of Wilson-Mikity syndrome as a rare complication of chorioamnionitis. This entity should raise concerns about decision making and counseling for patients with suspicious chorioamnionitis, such as requirement for tocolysis or intended preterm birth.

Roflumilast Fully Prevents Emphysema in Mice Chronically Exposed to Cigarette Smoke

There is a need for new agents capable of suppressing the inflammatory response in chronic obstructive pulmonary disease. This study evaluated the effects of roflumilast, a phosphodiesterase 4 (PDE4) inhibitor on acute lung inflammation and chronic lung changes in models of cigarette exposure in mice. Roflumilast was given orally either at 1 mg/kg (R1) or at 5 mg/kg (R5). In the acute model (five cigarettes for 20 minutes), bronchoalveolar lavage fluid (BALF) changes were investigated at 4 and 24 hours. In the chronic model (three cigarettes/day for 7 months), morphometric and biochemical parameters were assessed at 7 months. Acute exposure caused a fivefold increase in BALF neutrophils. Both doses of roflumilast partially prevented (by 30%) this increase. In addition, after smoke exposure, R1 increased BALF interleukin-10 by 79% and R5 by 129%. Chronic smoke exposure caused a 1.8-fold increase in lung macrophage density, emphysema, an increase of the mean linear intercept (+21%), a decrease of the internal surface area (-13%), and a drop (-13%) in lung desmosine content. R1 did not have any effect, whereas R5 prevented the increase in lung macrophage density by 70% and fully prevented the other changes. In addition, in the smoke-exposure group, 63% of the mice showed goblet cell metaplasia, and neither of the doses of roflumilast had any effect. This study shows for the first time that a PDE4 inhibitor partially ameliorates lung inflammation and fully prevents parenchymal destruction induced by cigarette smoke.

Occupational Health Hazards and Preventive Aspects in Welding

Welding, although not an industry in the strict sense in which the term is used, is in fact an ubiquitous process for the application of welding, is now so widespread that there is no metal industry or branch of engineering, where welding is not used in one form or the other. Occupational health hazards in welding pertain to visual hazards, exposure to metal oxide fumes and other fumes generated as a result of high intensity arc. Exposure to non-ionization radiation like U-V rays and infrared rays are discussed with particular reference to aluminium welding. Incidence of approximately 1.2 percent of ‘arc eyes’ of all eye injuries in metal fabrication is reported. OH complaints among welders show high incidence (41.3%) of conjunctival involvement compared to controls (12.9%). No evidence of infrared cataract has been found among the 41 welders with over 10 years of welding exposure. Chronic lung changes in 41 welders engaged in arc welding work having more than 10 years of exposure and 19 healthy unexposed males as control group were taken for study on random basis. Minimal restrictive and obstruction disability was observed among smoker welders only compared to non-smoker group. A case report of metal fume fever' due to inhalation of copper fumes is described. Preventive measures towards visual hazards and control of fumes in welding environment are discussed in detail.

Prediction of Abnormal Pulmonary Follow-up in Premature Infants

The article by Shennan and collaborators1 raises some interesting questions concerning the diagnosis of chronic lung disease and the predictability of respiratory outcome in early infancy. The first question addressed by the authors relates to the definition of bronchopulmonary dysplasia. This term was introduced by Northway et al2 in 1967 to describe a group of infants in whom severe chronic lung changes developed after prolonged mechanical ventilation and oxygen therapy. Most of these were infants with birth weights greater than 1000 g in whom chronic respiratory failure developed and whose chest radiographs appeared abnormal. In recent years, there has been an increase in the survival rate of infants with birth weights less than 1000 g, which has resulted in an increase in the population at risk for the development of chronic lung disease.

Methotrexate-induced sudden fatal pulmonary reaction

A teenage girl in bone marrow remission with acute lymphocytic leukemia died suddenly from pulmonary edema. She had taken her first oral dose of methotrexate and cyclophosphamide 10 hours previously when she was feeling well and was asymptomatic. One week previously she had received the last of four intrathecal injections of methotrexate. Autopsy showed marked pulmonary edema as well as chronic lung changes, as previously described in patients with methotrexate pneumonitis. There is usually at least a 12-day interval from the onset of administration of methotrexate to the onset of the lung toxicity. The authors suggest the patient was sensitized by the intrathecal methotrexate and then reacted with angioneurotic edema of the lung when given the first oral dose of methotrexate. Careful examination for infectious agents, including electron microscopy, was negative.

Radiographic manifestations of primary acquired hypogammaglobulinemia.

Radiographic examinations of 24 patients with primary acquired hypogammaglobulinemia were reviewed. Although all patients had chest examinations, the extent of other radiographic studies varied. Acute and/or chronic lung changes with obstructive lung disease, occasionally associated with bronchiectasis, were found in almost all cases. Most patients had sinusitis and more than half had splenomegaly. Small bowel changes included thickening of the valvulae conniventes or lymphonodular hyperplasia. Since lung disease, sinusitis, and splenomegaly were found in the majority of the patients, this combination of findings is presented as an occasionally useful triad in the diagnosis of primary acquired hypogammaglobulinemia.

Cystic Fibrosis of the Pancreas

HomeRadiologyVol. 46, No. 4 PreviousNext EditorialCystic Fibrosis of the PancreasPublished Online:Apr 1 1946https://doi.org/10.1148/46.4.412MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractWith the increasing knowledge of certain disease processes and the accumulation of data by various investigators, many conditions that were previously discovered only at the postmortem table are now being diagnosed in the living with relative frequency. Among these is cystic fibrosis of the pancreas. While this has been accepted as a clinical entity, actually it is in most instances a part of a generalized process consisting in fibrosis and insufficiency of the pancreas, glandular involvement, and chronic lung changes. These last, demonstrable roentgenographically, may establish the diagnosis.The work of Andersen (1) and of Black-fan and May (3) in 1938 did much to familiarize the medical profession with cystic disease of the pancreas as a disease entity. Their reports were the forerunners of a fairly numerous series by other workers who have added further details to our knowledge of the condition and the widespread changes associated with it.The etiology has not yet been satisfactorily established. Some have regarded the pancreatic changes as of congenital origin, but this theory has not met with general acceptance. A familial tendency has, however, been recorded by a number of observers. The disease is essentially one of early infancy, the average age of onset in one series of 35 cases (3) being two months, with death at eight months. Some patients survive longer, in which event a diagnosis of “celiac disease” is usually made.When death ensues shortly after birth, there is usually intestinal obstruction by thick mucilaginous meconium—so-called meconium ileus. If the child survives beyond this period, symptoms of chronic respiratory disease may so dominate the picture that the underlying condition may be missed entirely. In children living to six months or longer, the celiac syndrome-emaciation, abdominal distention, large fatty stools—becomes more obvious. At the same time the pulmonary changes persist and may be the immediate cause of death.Attwood and Sargent (2) have given an excellent description of the associated pulmonary lesions in cystic fibrosis of the pancreas. These consist, essentially, in a purulent bronchitis with bronchiectatic abscess formation and surrounding pneumonitis. The roentgen picture is one of infiltration throughout both lungs, decreasing toward the periphery, the greatest density occurring over the hilar areas. These changes suggest a chronic or subacute process rather than an acute one. Neuhauser (4), in a paper published in this issue of Radiology, recognizes two stages of pulmonary involvement: a pre-infection stage, which is characterized by emphysema and atelectasis secondary to obstructing phenomena, and a second stage of superimposed infection with the changes described above. Neuhauser gives, also, an excellent description of the roentgen features of meconium ileus associated with pancreatic insufficiency.Article HistoryPublished in print: Apr 1946 FiguresReferencesRelatedDetailsRecommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 46, No. 4 Metrics Altmetric Score PDF download