ABSTRACT
Congenital lung lesions are a rare group of developmental pulmonary abnormalities that are often first identified prenatally on routine second-trimester US. Congenital pulmonary airway malformation (CPAM) is the most common anomaly while others include bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and bronchial atresia. Clinical presentation is highly variable, ranging from apparent in utero resolution to severe mass effect with resultant hydrops fetalis and fetal demise. Differentiation among these lesions can be challenging because overlapping imaging features are often present. The roles of the radiologist are to identify key imaging findings that help in diagnosing congenital lung lesions and to recognize any ominous features that might require prenatal or perinatal intervention. High-resolution US and complementary rapid-acquisition fetal MRI provide valuable information necessary for lesion characterization. Postnatal US and CT angiography are helpful for lesion evaluation and for possible surgical planning. This article reviews the embryology of the lungs, the normal prenatal imaging appearance of the thorax and its contents, and the prenatal and neonatal imaging characteristics, prognosis and management of various congenital lung lesions.
Subject(s)
Bronchopulmonary Sequestration , Cystic Adenomatoid Malformation of Lung, Congenital , Pneumonia , Respiratory System Abnormalities , Bronchopulmonary Sequestration/diagnostic imaging , Bronchopulmonary Sequestration/pathology , Cystic Adenomatoid Malformation of Lung, Congenital/diagnosis , Cystic Adenomatoid Malformation of Lung, Congenital/pathology , Cystic Adenomatoid Malformation of Lung, Congenital/surgery , Female , Humans , Infant, Newborn , Lung/diagnostic imaging , Lung/pathology , Pregnancy , Respiratory System Abnormalities/diagnostic imaging , Respiratory System Abnormalities/pathology , Ultrasonography, Prenatal/methodsABSTRACT
Midface dysgenesis is a feature of more than 200 genetic conditions in which upper airway anomalies frequently cause respiratory distress, but its etiology is poorly understood. Mouse models of Apert and Crouzon craniosynostosis syndromes exhibit midface dysgenesis similar to the human conditions. They carry activating mutations of Fgfr2, which is expressed in multiple craniofacial tissues during development. Magnetic resonance microscopy of three mouse models of Apert and Crouzon syndromes revealed decreased nasal passage volume in all models at birth. Histological analysis suggested overgrowth of the nasal cartilage in the two Apert syndrome mouse models. We used tissue-specific gene expression and transcriptome analysis to further dissect the structural, cellular and molecular alterations underlying midface and upper airway dysgenesis in Apert Fgfr2+/S252W mutants. Cartilage thickened progressively during embryogenesis because of increased chondrocyte proliferation in the presence of Fgf2 Oral epithelium expression of mutant Fgfr2, which resulted in a distinctive nasal septal fusion defect, and premature facial suture fusion contributed to the overall dysmorphology. Midface dysgenesis in Fgfr2-related craniosynostosis is a complex phenotype arising from the combined effects of aberrant signaling in multiple craniofacial tissues.
Subject(s)
Cell Cycle , Craniosynostoses/embryology , Face/abnormalities , Organ Specificity , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Respiratory System Abnormalities/embryology , Respiratory System Abnormalities/pathology , Acrocephalosyndactylia/pathology , Animals , Cartilage/pathology , Cell Proliferation , Chondrocytes/pathology , Cranial Sutures/pathology , Craniofacial Dysostosis/embryology , Craniofacial Dysostosis/pathology , Craniosynostoses/pathology , Disease Models, Animal , Embryo, Mammalian/abnormalities , Embryo, Mammalian/pathology , Face/embryology , Face/pathology , Gene Expression Regulation, Developmental , Mice, Inbred C57BL , Mice, Mutant Strains , Nose/abnormalities , Nose/embryology , Nose/pathology , Receptor, Fibroblast Growth Factor, Type 2/geneticsABSTRACT
The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway; this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2; on the contrary, they maintain their staminality profile.
Subject(s)
Mesenchymal Stem Cells/metabolism , Respiratory System Abnormalities , SARS-CoV-2/physiology , Transcriptome , COVID-19/genetics , COVID-19/metabolism , COVID-19/pathology , Case-Control Studies , Cells, Cultured , Gene Expression Profiling , Host-Pathogen Interactions/genetics , Humans , Infant , Lung/abnormalities , Lung/metabolism , Lung/pathology , Male , Mesenchymal Stem Cells/pathology , Mesenchymal Stem Cells/virology , RNA-Seq , Respiratory System Abnormalities/genetics , Respiratory System Abnormalities/pathology , Respiratory System Abnormalities/virologyABSTRACT
Congenital pulmonary airway malformations (CPAMs) are rare lung abnormalities that result in cyst formation and are associated with respiratory distress in infants and malignant potential in adults. The pathogenesis of CPAMs remains unknown but data suggest disruption of the normal proximo-distal programme of airway branching and differentiation. Here, we demonstrate that adult human CPAM are lined with epithelium that retains SOX-2 and thyroid transcription factor-1 immunohistochemical markers, characteristic of the developing lung. However, RALDH-1, another key marker, is absent. This suggests a more complex aetiology for CPAM than complete focal arrest of lung development and may provide insight to the associated risk of malignancy.
Subject(s)
Lung/embryology , Respiratory Mucosa/metabolism , Respiratory System Abnormalities/metabolism , Respiratory System Abnormalities/pathology , Adult , Aldehyde Dehydrogenase 1 Family/metabolism , Biomarkers/metabolism , Cell Differentiation , DNA-Binding Proteins/metabolism , Humans , In Vitro Techniques , Retinal Dehydrogenase/metabolism , SOXB1 Transcription Factors/metabolism , Transcription Factors/metabolismABSTRACT
Early enzyme replacement therapy (ERT) improve long-term outcomes in patients with infantile-onset Pompe disease (IOPD). Our cohort of patients with IOPD at Taipei Veterans General Hospital (TVGH) joined Taiwan Pompe newborn screening program from 2008, testing more than one million newborns until 2018. By 2010, we had established rapid diagnostic strategies. Now, the average age of ERT initiation starts at an average age of <10 days-old, the earliest group in the world. However, they still presented some airway problems. We present a retrospective study focused on airway abnormalities in these patients along 8 years of observation. Fifteen patients with IOPD, who received very early treatment at a mean age of 8.94 ± 3.75 days, underwent flexible bronchoscopy (FB) for dynamic assessment of the whole airway. Long-term clinical outcomes and relevant symptoms of the upper airway were assessed. All patients in the study had varying degrees of severity of upper airway abnormalities and speech disorders. The three oldest children (Age 94, 93, and 88 months, respectively) had poor movement of the vocal cords with reduced abduction and adduction and had silent aspiration of saliva through the glottis during respiration. This is the largest cohort study presented to date about airway abnormalities in very early treated patients with IOPD patients by FB. Despite very early treatment, we observed upper airway abnormalities in these IOPD patients. In IOPD, upper airway abnormalities seem inevitable over time. We suggest early and continuous monitoring for all IOPD patients, even with early and regular treatment.
Subject(s)
Bronchoscopy/methods , Glycogen Storage Disease Type II/complications , Respiratory System Abnormalities/pathology , Child , Child, Preschool , Enzyme Replacement Therapy , Female , Humans , Infant , Infant, Newborn , Male , Prognosis , Respiratory System Abnormalities/etiology , Respiratory System Abnormalities/therapy , Retrospective StudiesABSTRACT
Pulmonary malformations are rare disorders, with cystic and pseudocystic pulmonary malformations (CPPM) the most frequent, and constitute the first cause of lobectomy in children <1â¯year of age. Morphological overlap of congenital cystic pulmonary lesions might correspond to a spectrum of lesions in which bronchial atresia is a common etiopathogenetic mechanism. We aimed to report the frequency of CPPM resected in a tertiary-level hospital and to evaluate the degree of agreement between presurgical and anatomopathological diagnoses. We studied 44 surgical pieces with a diagnosis of CPPM received at the Pathology Service from 2009 to 2014, resected from 39 patients, 51.3 % males, with a median age of 16.8â¯months. Up to 69.2% of the patients had adenomatoid malformation of pulmonary airway (AMPA), with type 2 the most frequent (55.5%). Pulmonary sequestration was present in 15.4% of patients; in two cases the diagnosis was an incidental finding during surgery for the repair of a diaphragmatic hernia. Congenital lobar hyperinflation (CLH) occurred in 7.6% cases. Bronchogenic cyst (BC) was present in 7.6% cases. Presurgical and anatomopathological diagnoses in all patients coincided in 71.8% of cases. Kappa coefficient was 0.56 for global concordance in patients with AMPA, and 0.72, 0.64, 0.37 and 0.33 for CLH, BC, and types 1 and 2 AMPA, respectively. This relatively low interobserver agreement could reflect the low reproducibility of diagnoses used in the current nomenclature. Thus, the new nomenclature must be promoted in order to allow for better reproducibility and greater clinico-pathological concordance. The anatomopathological analysis must include the intentional search for bronchial atresia.
Subject(s)
Pulmonary Surgical Procedures/methods , Respiratory System Abnormalities/diagnosis , Respiratory System Abnormalities/surgery , Adolescent , Bronchogenic Cyst/diagnosis , Bronchogenic Cyst/pathology , Bronchogenic Cyst/surgery , Bronchopulmonary Sequestration/diagnosis , Bronchopulmonary Sequestration/pathology , Bronchopulmonary Sequestration/surgery , Child , Child, Preschool , Cross-Sectional Studies , Cystic Adenomatoid Malformation of Lung, Congenital/diagnosis , Cystic Adenomatoid Malformation of Lung, Congenital/pathology , Cystic Adenomatoid Malformation of Lung, Congenital/surgery , Female , Humans , Infant , Infant, Newborn , Male , Observer Variation , Pulmonary Emphysema/congenital , Pulmonary Emphysema/diagnosis , Pulmonary Emphysema/pathology , Pulmonary Emphysema/surgery , Respiratory System Abnormalities/pathology , Retrospective Studies , Tertiary Care CentersABSTRACT
BACKGROUND: At fetal MR, congenital lung lesions are usually T2 hyperintense with respect to normal lung parenchyma. Some lesions, however, demonstrate unusual patterns of T2 hypointensity, sometimes in a rosette-like pattern. These lesions usually present a diagnostic conundrum. OBJECTIVE: To evaluate the imaging findings and pathological characterization of fetal solid lung lesions with elements showing T2-hypointense signal with respect to lung. MATERIALS AND METHODS: This is a retrospective study of lung lesions with elements showing T2 hypointensity treated prenatally and postnatally at our center and with available pathological evaluation. Prenatal imaging evaluation included US and MR; postnatal evaluation consisted of pathological examination of the lesion. We also performed prenatal and postnatal chart review. RESULTS: Six cases met study criteria. Areas of decreased echogenicity/T2-hypointense signal were more conspicuous at MR than US. At pathology, these areas correlated with immature parenchymal development and increased mesenchymal tissue. Five of these lesions were congenital pulmonary airway malformations (CPAM); one was a congenital peribronchial myofibroblastic tumor (CPMT). The lesions did not significantly change in size after steroid administration. They were all large in volume and were associated with increased amniotic fluid. All cases of CPAM underwent premature delivery (one of them weeks after fetal surgical resection of the lesion for worsening hydrops); the fetus with CPMT was delivered at term. The neonate with CPMT succumbed shortly after birth secondary to lung hypoplasia; the remaining five neonates survived. CONCLUSION: The differential diagnoses of prenatal lung lesions that contain unusual T2-hypointense elements include CPAM and CPMT. The T2-hypointense areas appear to correlate with increasing degree of immaturity at histology. None of the lesions significantly changed in size after prenatal administration of steroids. All cases with CPAM lesions did well despite persistent polyhydramnios and premature birth. The single case of CPMT, however, resulted in neonatal demise shortly after birth secondary to pulmonary hypoplasia. It is important that fetal radiologists, obstetricians and fetal surgeons alike are aware of these lesions so that appropriate diagnosing and parental counseling can be reached.
Subject(s)
Lung/abnormalities , Magnetic Resonance Imaging/methods , Respiratory System Abnormalities/diagnostic imaging , Ultrasonography, Prenatal/methods , Diagnosis, Differential , Female , Humans , Infant, Newborn , Pregnancy , Prenatal Diagnosis , Respiratory System Abnormalities/pathology , Respiratory System Abnormalities/surgeryABSTRACT
OBJECTIVES: The congenital pulmonary airway malformation volume ratio (CVR) is a widely used sonographic measure of relative mass size in fetuses with lung malformations. The purposes of this study were to examine serial CVR measurements to understand longitudinal growth patterns and to determine correlation with postnatal imaging. METHODS: An institutional review board-approved retrospective review was performed on fetuses referred for an echogenic lung malformation between 2002 and 2014. For each fetus, the CVR was prospectively calculated using 2D ultrasound and followed with advancing gestation. RESULTS: Based on 40 fetuses, the mean initial CVR was 0.51 ± 0.07 at 20.5 ± 0.3 weeks of gestation. The CVR increased after 24 weeks of gestation (p = 0.0014), peaking at a CVR of 0.96 ± 0.11 at 25.5 ± 0.05 weeks, followed by a significant decrease in the CVR to 0.43 ± 0.07 prior to term (p < 0.0001). However, approximately one third showed no appreciable increase in size. The mean CVR was significantly correlated with postnatal chest computed tomography (CT) size dimensions (p = 0.0032) and likelihood for lung resection (p = 0.0055). CONCLUSIONS: Fetal lung malformations tend to follow one of two distinct growth patterns, characterized by either (1) a maximal CVR between 25 and 26 weeks of gestation or (2) minimal change in relative growth. The mean CVR correlates with postnatal CT size and operative management.
Subject(s)
Fetal Diseases/diagnostic imaging , Lung/abnormalities , Lung/diagnostic imaging , Monitoring, Physiologic/methods , Respiratory System Abnormalities/diagnostic imaging , Female , Fetal Diseases/pathology , Gestational Age , Humans , Infant, Newborn , Organ Size , Pregnancy , Pregnancy Outcome , Prognosis , Respiratory System Abnormalities/pathology , Retrospective Studies , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: The purpose is to describe fetal MR and US findings of congenital overinflation (CO) and to correlate with postnatal outcome. METHODS: Two radiologists reviewed fetal MR and US images in 25 fetuses diagnosed with CO. Lesion size, appearance, location, and presence of hydrops were documented. Chart review was performed for pregnancy outcome, postnatal imaging, interventions, histopathology, and clinical outcome. RESULTS: All lesions demonstrated primarily homogeneous increased echogenicity and MR signal with absent pulmonary vascular distortion. A tubular cystic hilar structure was consistent with a dilated bronchus (68% MR, 25% US). The right lower (32%) and left lower (23%) lobes were most commonly involved. Two cases with central bronchial obstruction resulted in perinatal demise. Of 23 live births, 17 were asymptomatic, 1 symptomatic, and 5 lost to follow-up. Postnatal CT was performed in 17 of 18 patients confirming CO. Histopathology in nine patients revealed bronchial anomalies with hyperinflated (n = 7) or polyalveolar lung (n = 2). Nine patients were observed and remained asymptomatic. CONCLUSIONS: Fetal MR and US demonstrate a consistent pattern of imaging findings in fetuses with CO. Many cases are asymptomatic and can be managed with nonsurgical conservative therapy. CO because of central bronchial obstruction is associated with a guarded prognosis. © 2016 John Wiley & Sons, Ltd.
Subject(s)
Airway Obstruction/diagnostic imaging , Bronchi/diagnostic imaging , Lung/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Respiratory System Abnormalities/diagnostic imaging , Airway Obstruction/congenital , Airway Obstruction/pathology , Airway Obstruction/surgery , Bronchi/abnormalities , Bronchi/pathology , Bronchi/surgery , Female , Humans , Infant, Newborn , Lung/abnormalities , Lung/pathology , Lung/surgery , Magnetic Resonance Imaging , Male , Pneumonectomy , Pregnancy , Pregnancy Outcome , Prenatal Diagnosis , Pulmonary Emphysema/congenital , Pulmonary Emphysema/pathology , Pulmonary Emphysema/surgery , Respiratory System Abnormalities/pathology , Respiratory System Abnormalities/surgery , Retrospective Studies , Ultrasonography, PrenatalABSTRACT
OBJECTIVES: Congenital pulmonary airway malformation (CPAM) is an uncommon congenital abnormality of the lungs that generally presents during prenatal period or early childhood. In this study, we aimed to evaluate clinical and pathologic findings of the children with CPAMs who were referred to our center between 1992 and 2011. MATERIAL AND METHODS: We reviewed 19 children with CPAM, who were diagnosed and treated at the Izmir Dr. Behçet Uz Children's Hospital between 1992 and 2011. All of them are alive and have been still followed up by our center. RESULTS: The study population consisted of 9 boys (47.4%) and 10 girls (52.6%) with a mean age of 3.26 (1 month - 13 years). Most newborns had respiratory distress, while recurrent pulmonary infections were detected in older children. Surgical treatment was performed on patients with subtypes I (n = 4; 21.1%), II (n = 8; 42.1%), III (n = 5; 26.3%), and IV (n = 2; 10.5%). In 13 cases (63.4%), lesions were located in the right lung and in almost all cases lesions were confined to one lobe. A one-month- old child with type I CPAM had multiple lesions involving two lobes and in only a newborn with type II CPAM, lesions were located bilaterally. There was no type 0 cases in this series. All cases were treated with lobectomy without any complication. CONCLUSION: In the present study, a realistic comprehensive picture of CPAM in a central children's hospital has been provided. In addition, we want to emphasize that complications and unnecessary medical treatment could be reduced with early surgery.
Subject(s)
Lung/pathology , Respiratory System Abnormalities/pathology , Adolescent , Child , Child, Preschool , Cystic Adenomatoid Malformation of Lung, Congenital/complications , Cystic Adenomatoid Malformation of Lung, Congenital/pathology , Female , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/pathology , Lung/abnormalities , Male , Respiratory System Abnormalities/complications , Respiratory System Abnormalities/diagnosis , Retrospective Studies , Tomography, X-Ray Computed/methodsABSTRACT
Gene overexpression has been identified as a primary determining factor for the distinct Down syndrome (DS) phenotypes. Previous genetic research has identified a spectrum of gene expressions responsible for many of the observed traits in DS patients including cardiovascular, brain, and GI anomalies. However, the molecular/genetic basis underlying pulmonary anomalies are yet to be identified, even though respiratory complications represent the leading cause of morbidity and mortality in DS patients. In this article, we will discuss the Etiopathogenesis and spectrum of pulmonary anomalies in DS patients.
Subject(s)
Down Syndrome/complications , Down Syndrome/pathology , Respiratory System Abnormalities/genetics , Respiratory System Abnormalities/pathology , HumansABSTRACT
BACKGROUND: Most pulmonary conditions reduce FVC, but studies of patients with combined pulmonary fibrosis and emphysema demonstrate that reductions in FVC are less than expected when these two conditions coexist clinically. RESEARCH QUESTION: Do interstitial lung abnormalities (ILAs), chest CT imaging findings that may suggest an early stage of pulmonary fibrosis in individuals with undiagnosed disease, affect the association between emphysema and FVC? STUDY DESIGN AND METHODS: Measures of ILA and emphysema were available for 9,579 and 5,277 participants from phases 1 (2007-2011) and 2 (2012-2016) of the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study (COPDGene), respectively. ILA were defined by Fleischner Society guidelines. Adjusted linear regression models were used to assess the associations and interactions among ILA, emphysema, measures of spirometry, and lung function. RESULTS: ILA were present in 528 (6%) and 580 (11%) of participants in phases 1 and 2 of COPDGene, respectively. ILA modified the association between emphysema and FVC (P < .0001 for interaction) in both phases. In phase 1, in those without ILA, a 5% increase in emphysema was associated with a reduction in FVC (-110 mL; 95% CI, -121 to -100 mL; P < .0001); however, in those with ILA, it was not (-11 mL; 95% CI, -53 to 31; P = .59). In contrast, no interaction was found between ILA and emphysema on total lung capacity or on diffusing capacity of carbon monoxide. INTERPRETATION: The presence of ILA attenuates the reduction in FVC associated with emphysema.
Subject(s)
Emphysema , Pulmonary Emphysema , Pulmonary Fibrosis , Respiratory System Abnormalities , Emphysema/pathology , Humans , Lung/pathology , Pulmonary Emphysema/diagnostic imaging , Pulmonary Emphysema/pathology , Respiratory System Abnormalities/pathology , Smokers , SpirometryABSTRACT
Cysteinyl leukotriene (cysLT) overproduction and eosinophil activation are hallmarks of aspirin-exacerbated respiratory disease (AERD). However, pathogenic mechanisms of AERD remain to be clarified. Here, we aimed to find the significance of transforming growth factor beta 1 (TGF-ß1) in association with cysteinyl leukotriene E4 (LTE4) production, leading to eosinophil degranulation. To evaluate levels of serum TGF-ß1, first cohort enrolled AERD (n = 336), ATA (n = 442) patients and healthy control subjects (HCs, n = 253). In addition, second cohort recruited AERD (n = 34) and ATA (n = 25) patients to investigate a relation between levels of serum TGF-ß1 and urinary LTE4. The function of TGF-ß1 in LTE4 production was further demonstrated by ex vivo (human peripheral eosinophils) or in vivo (BALB/c mice) experiment. As a result, the levels of serum TGF-ß1 were significantly higher in AERD patients than in ATA patients or HCs (P = .001; respectively). Moreover, levels of serum TGF-ß1 and urinary LTE4 had a positive correlation (r = 0.273, P = .037). In the presence of TGF-ß1, leukotriene C4 synthase (LTC4S) expression was enhanced in peripheral eosinophils to produce LTE4, which sequentially induced eosinophil degranulation via the p38 pathway. When mice were treated with TGF-ß1, significantly induced eosinophilia with increased LTE4 production in the lung tissues were noted. These findings suggest that higher levels of TGF-ß1 in AERD patients may contribute to LTE4 production via enhancing LTC4S expression which induces eosinophil degranulation, accelerating airway inflammation.
Subject(s)
Asthma, Aspirin-Induced/blood , Glutathione Transferase/urine , Respiratory System Abnormalities/blood , Transforming Growth Factor beta1/blood , Adult , Animals , Aspirin/adverse effects , Aspirin/therapeutic use , Asthma, Aspirin-Induced/genetics , Asthma, Aspirin-Induced/pathology , Eosinophils/metabolism , Eosinophils/pathology , Female , Gene Expression Regulation/drug effects , Humans , Inflammation/blood , Inflammation/chemically induced , Inflammation/genetics , Inflammation/pathology , Leukotriene E4/biosynthesis , Leukotriene E4/blood , Leukotriene E4/genetics , Male , Mice , Middle Aged , Receptors, Leukotriene/metabolism , Respiratory System/drug effects , Respiratory System/metabolism , Respiratory System/pathology , Respiratory System Abnormalities/chemically induced , Respiratory System Abnormalities/genetics , Respiratory System Abnormalities/pathology , Transforming Growth Factor beta1/genetics , p38 Mitogen-Activated Protein Kinases/geneticsABSTRACT
RATIONALE: Congenital pulmonary airway malformation (CPAM) is a rare developmental deformity of the lower respiratory tract. The disease occurs more in newborns. However, on rare occasions, CPAM can be found in adults. Radiologic features of CPAM include cystic or solid mass pattern. In an elderly patient, CPAM can be easily misdiagnosed as lung cancer. PATIENT CONCERNS: A 66-year old woman was admitted with complaints of chronic cough, expectoration. Her past history was unremarkable with no history of tuberculosis or smoking. Physical examination was normal. Computerized tomography of the chest showed an irregular cystic lesion in right lower lobe. DIAGNOSIS: Histopathological results confirmed the diagnosis of CPAM. INTERVENTION: The right pulmonary wedge resection was performed via thoracoscopic surgery. OUTCOMES: On follow up 1 year later, the patient is asymptomatic. LESSONS: CPAM is rare in adults, and imaging cannot accurately distinguish CPAM from thin-walled cystic lung cancer. Hence, histopathology is mandatory to confirm the diagnosis.
Subject(s)
Respiratory System Abnormalities/diagnosis , Respiratory System Abnormalities/surgery , Aged , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Lung/pathology , Lung/surgery , Lung Neoplasms/diagnosis , Respiratory System Abnormalities/pathologyABSTRACT
HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.
Subject(s)
HIV Infections/complications , HIV/immunology , Inflammation Mediators/immunology , Respiratory System Abnormalities/etiology , HIV Infections/immunology , HIV Infections/virology , Humans , Inflammation Mediators/metabolism , Respiratory System Abnormalities/metabolism , Respiratory System Abnormalities/pathologyABSTRACT
Sandifer's syndrome is a gastrointestinal disorder with neurological features. It is characterized by reflex torticollis following deglutition in patients with gastroesophageal reflux and/or hiatal hernia. The authors believe that neurological manifestations of the syndrome are the consequence of vagal reflex with the reflex center in nucleus tractus solitarii (NTS). Three models for the neuroanatomical basis of the hypothetic reflex arc are presented. In the first one the hypothetic reflex arc is based on the classic hypothesis of two components nervus accessorius (n.XI) - radix cranialis (RC) and radix spinalis (RS) The nervous impulses are transmitted by nervus vagus (n.X) general visceral afferent (GVA) fibers to NTS situated in medulla oblongata, then by interneuronal connections on nucleus ambiguus (NA) and nucleus dorsalis nervi vagi (NDX). Special visceral efferent fibers (SVE) impulses from NA are in part transferred to n.XI ramus externus (RE) (carrying the majority of general somatic efferent (GSE) fibers) via hypothetic anastomoses in the region of foramen jugulare. This leads to contraction of trapezius and sternocleidomastoideus muscles, and the occurrence of intermittent torticollis. In the second suggested neuroanatomical model the hypothetic reflex arc is organized in the absence of n.XI RC, the efferent part of the reflex arc continues as NA, which is motor nucleus of nervus glossopharyngeus (n.IX) and n.X in this case while distal roots of n.XI that appear at the level of the olivary nucleus lower edge represent n.X roots. In the third presented model the hypothetic reflex arc includes no jugular transfer and could be realized via interneuronal connections directly from NTS to the spinal motoneurons within nucleus radicis spinalis nervi accessorii (NRS n.XI) or from NA to NRS n.XI. The afferent segment of the postulated reflex arc in all three models is mediated via n.X. We conclude that Sandifer's syndrome is a clinical manifestation of another vagal reflex that could be termed a "vagocervical" or "esophagocervical" reflex, based on the neuroanatomical hypotheses elaborated in this paper.
Subject(s)
Brain/pathology , Reflex , Respiratory System Abnormalities/pathology , Vagus Nerve/pathology , Humans , Models, Biological , Models, Neurological , Models, Theoretical , Motor Neurons/pathology , Neurons/metabolism , Respiratory System Abnormalities/etiology , SyndromeABSTRACT
OBJECTIVES: To characterize the frequency of airway anomalies in patients with 22q11.2 deletion syndrome (22q11DS). METHODS: Retrospective review of patients with 22q11DS who had undergone microlaryngoscopy/bronchoscopy (MLB) for aerodigestive symptoms at a tertiary care children's hospital from 2011 to 2016. RESULTS: Thirty patients underwent an MLB due to the following indications: aspiration (11), stridor (10), chronic respiratory failure due to ventilator dependence (8), and difficult intubation (1). Median age at MLB was 6.5 months (range, 0.25-32 months). Forty airway anomalies were identified in 20 (66%) patients. Laryngomalacia (10), tracheomalacia (8), and bronchomalcia (8) were the most common intraoperative findings, followed by laryngeal cleft (5), anterior glottic web (5), subglottic stenosis (3), and subglottic cysts (1). Synchronous airway anomalies were common and identified in 11 (55%) of the patients who had identified anomalies on MLB. Nineteen of the 20 patients required operative intervention due to the anomalies identified. CONCLUSIONS: Structural airway abnormalities are common in children with 22q11DS undergoing MLB, and synchronous anomalies can frequently exist. Providers caring for children with 22q11DS should be vigilant about airway evaluation when aerodigestive symptoms are present.
Subject(s)
DiGeorge Syndrome/complications , DiGeorge Syndrome/pathology , Respiratory System Abnormalities/epidemiology , Bronchoscopy , Child, Preschool , DiGeorge Syndrome/surgery , Female , Humans , Incidence , Infant , Infant, Newborn , Laryngoscopy , Male , Respiratory System Abnormalities/pathology , Respiratory System Abnormalities/surgery , Retrospective StudiesABSTRACT
We report a 9-month-old female infant presenting, on the 15th day of life, left tibial agenesis with ectrodactyly, right talipes equinovarus, syndactyly of the second and the third toes of the right foot, an incomplete split right foot, left fibular hypoplasia, bronchial stenosis/hypoplasia, and coarctation of the aortic arch. To the best of our knowledge, coarctation of the aortic arch and bronchial stenosis/hypoplasia have never been reported in the tibial agenesis-ectrodactyly syndrome.
Subject(s)
Abnormalities, Multiple/pathology , Aortic Coarctation/pathology , Clubfoot/pathology , Female , Humans , Infant, Newborn , Respiratory System Abnormalities/pathology , SyndromeABSTRACT
Oculoauriculofrontonasal syndrome was the subset of patients with oculo-auriculo-vertebral spectrum and frontonasal malformation. Radiographic evidence of tracheal duplication was documented in a male infant with oculoauriculofrontonasal syndrome. Although previously unreported in oculoauriculofrontonasal syndrome, airway anomalies in our case can be attributed to the oculo-auriculo-vertebral component of the oculoauriculofrontonasal syndrome.
Subject(s)
Abnormalities, Multiple/pathology , Eye Abnormalities/pathology , Female , Humans , Infant, Newborn , Male , Nose/abnormalities , Nose/pathology , Respiratory System Abnormalities/pathology , Spine/abnormalities , Spine/pathology , SyndromeABSTRACT
BACKGROUND: Previous studies support good intra- and interobserver agreements for endoscopic evaluation of various upper respiratory tract (URT) diseases in horses. However, these studies mainly assessed resting endoscopic examination videos and/or focussed on a single URT abnormality. OBJECTIVES: To estimate intra- and interobserver agreement for identification and grading of all URT abnormalities from resting and overground endoscopy (OGE) videos of Thoroughbreds. STUDY DESIGN: Blinded, fully crossed design. METHODS: Resting and OGE URT videos for n = 43 Thoroughbreds were retrospectively chosen based on identification of common URT disorders. The videos were randomly evaluated in duplicate by 4 raters blinded to all information including prior URT disorder(s) diagnosis. Abnormalities were graded using well-described ordinal scales. Intra- and interobserver agreements were estimated using Cohen's weighted κ and Krippendorff's α, respectively. RESULTS: Intraobserver agreement was perfect/nearly perfect for arytenoid symmetry at exercise, epiglottic entrapment and epiglottic retroversion, substantial for arytenoid asymmetry at rest, palatal dysfunction (PD), medial deviation of the aryepiglottic folds (MDAF), pharyngeal mucus and epiglottic grade at exercise and moderate for vocal fold collapse (VFC), ventromedial luxation of the apex of the corniculate process of the arytenoid (VLAC), nasopharyngeal collapse (NPC) and epiglottic grade at rest. Interobserver agreement was substantial for arytenoid symmetry at exercise and PD and moderate for arytenoid asymmetry at rest, MDAF, VLAC and epiglottic entrapment. It was only fair for VFC, epiglottic grade at exercise, epiglottic retroversion, pharyngeal mucus and NPC and poor for epiglottic grade at rest. MAIN LIMITATIONS: Sample size was insufficient to allow assessment of the effect of one abnormality on the grading of another abnormality. CONCLUSIONS: Observers were consistent in grading URT disorders. However, significant disparity in grading existed between observers for some conditions affecting reliability.