Recurrent Episodes Of Infection Research Articles

Prolonged antibiotic treatment for infected low flow vascular malformations.

Infection in low flow malformations is difficult to diagnose and treat. Initial presentation can be followed by cycles of recurrent infection lasting several years. The optimal duration of antibiotic therapy to prevent recurrence of infection has not been established. All cases of infection in low flow malformations at the Royal Children's Hospital over a ten-year period were reviewed. Clinical markers of infection and duration of initial antibiotic treatment were correlated with the development of recurrent episodes of infection. Twenty-one patients met criteria for inclusion. Nineteen were diagnosed as lymphatic malformations and two as venous malformations. The majority of patients (13 or 62%) received a prolonged course of six weeks or more of antibiotics. Eleven (52%) patients went on to have recurrent infections, but these were significantly less likely to be in those treated with a long course of antibiotics (Fisher's exact test, p=0.026). In only 12 of 21 cases could a bacterium be grown. Elevated CRP was the most consistent abnormal laboratory finding in infection. Longer courses of antibiotics reduce the risk of recurrent infection in low-flow vascular malformations. We recommend an antibiotic course of three months or more at the initial presentation of infection in a low flow malformation. Elevated CRP is the most sensitive test for diagnosis of infection in low-flow malformations. Treatment study. III.

Multi-drug resistant Vibrio species isolated from abattoir effluents in Nigeria.

The antibiogram of Vibrio species isolated from abattoir effluents in the Niger Delta region of Nigeria was investigated in lieu of their public health significance. Vibrio species were isolated and identified using standard microbiological and molecular techniques; while antibiogram of isolates was tested and interpreted according to the disc diffusion method described by Clinical Laboratory Standards Institute. Forty eight (48) out of 150 presumptive isolates (32%) were confirmed to be Vibrio spp. by PCR; of this number (48), 23(47.9%) were V. cholerae, 11(22.9%) V. fluvialis, 8(16.7%) V. vulnificus and 6(12.5%) V. parahaemolyticus. The antibiogram reveals that Vibrio species were generally resistant to ampicillin (60-67%), trimethoprim (80-100%) and tetracycline (60-83%); whereas they were sensitive to ceftriaxone (86-100%), the aminoglycosides (67-100%), imipenem (86-100%), ofloxacin (83-100%) and chloramphenicol (67-100%). The isolates exhibited multiple antibiotic resistance (MAR) with an average MAR index of 0.23. The study demonstrated that abattoir effluents are important reservoirs for multidrug resistant Vibrio species that could be considerable contributors to the recurrent episodes of epidemic cholera and non-Vibrio cholerae infections in Nigeria.

Hemorheological alterations in sickle cell anemia and their clinical consequences - The role of genetic modulators.

Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis. The disease presents with high clinical heterogeneity characterized by chronic hemolysis, recurrent episodes of vaso-oclusion and infection. This work aimed to characterize by in silico studies some genetic modulators of severe hemolysis and stroke risk in children with SCA, and understand their consequences at the hemorheological level.Association studies were performed between hemolysis biomarkers as well as the degree of cerebral vasculopathy and the inheritance of several polymorphic regions in genes related with vascular cell adhesion and vascular tonus in pediatric SCA patients. In silico tools (e.g. MatInspector) were applied to investigate the main variant consequences.Variants in vascular adhesion molecule-1 (VCAM1) gene promoter and endothelial nitric oxide synthase (NOS3) gene were significantly associated with higher degree of hemolysis and stroke events. They potentially modify transcription factor binding sites (e.g. VCAM1 rs1409419_T allele may lead to an EVI1 gain) or disturb the corresponding protein structure/function. Our findings emphasize the relevance of genetic variation in modulating the disease severity due to their effect on gene expression or modification of protein biological activities related with sickled erythrocyte/endothelial interactions and consequent hemorheological abnormalities.

Phenotypic switch: The enigmatic white-gray-opaque transition system of Candida albicans

Candida albicans represents the most common commensal and opportunistic fungal pathogen colonizing humans. As a member of the normal microflora, it is present on the skin and the mucous membranes of the upper respiratory tract, gastrointestinal tract and female genital tracts. It is therefore not transmitted. It lies in wait for a change in some aspect of the host physiology that normally suppress growth and invasiveness through an enigmatic phenomenon called Phenotypic Switch System or White-Opaque Transition. This system involves reversible and heritable switching between alternative cellular phenotypes. White–opaque switching in Candida albicans was first discovered in 1987. This was initially identified in strain WO-1. Switching has been demonstrated to occur at sites of infection and to occur between recurrent episodes of infection in select cases esp. AIDS and diabetes.

Nasal Crust in a Case of Hypohidrotic Ectodermal Dysplasia

Hypohidrotic ectodermal dysplasia is a hereditary syndrome characterized mainly by the triad of less hair, less sweat and less teeth. It is associated with hypoplasia of the ectoderm caused by a genetic abnormality, and treatment remains mainly symptomatic. I encountered a case in a boy who presented with rhinostenosis at one month after birth. There were no anatomic abnormalities of the nasal cavity, however, the entire nasal cavity was filled with crust associated with atrophic nasal inflammation. Nose breathing was disturbed because of the pervasive crust and the child developed recurrent episodes of upper respiratory tract infection with a bad odor of the nasal mucus. Provision of care to prevent nasal crust formation for 4 years 6 months at the outpatient department led to improvement of the nose breathing and the bad odor of the nasal mucus. Herein, I report the method and the outcome.

Prevalence of Pelvic Incontinence in Patients With Cystic Fibrosis.

Cystic fibrosis (CF) patients are at risk for developing pelvic (urinary and/or fecal) incontinence due to progressive weakness of pelvic floor muscles secondary to recurrent episodes of coughing and respiratory infections. Many patients do not bring these symptoms to the attention of their health care providers because of social embarrassment and lack of knowledge of available effective treatment. Several studies have identified the prevalence of incontinence in CF adults and adolescents. However, few studies identified the problem in children with CF. Our study aims are to identify the prevalence of pelvic incontinence in CF patients aged 6 to 21 years, to identify the correlation between incontinence and severity of lung disease, and to help develop treatment strategy in collaboration with physical therapy to address these issues.

Medical management of primary vesicoureteric reflux: A changing trend: Single institute experience with 45 patients (77 renal units) over 2 years

Background: The management of vesicoureteric reflux (VUR) has undergone a radical change from initial ureteric reimplantation to a more conservative approach. Several studies have demonstrated the validity of this concept by evaluating the role of antibiotic prophylaxis. Recent randomized trials have shown no proven benefits of long-term antibiotic prophylaxis. Objective: The objective of this article is to review the outcome of conservative management of VUR with antibiotic prophylaxis over a period of 2-year. Materials and Methods: A prospective observational study for 2 years was performed in children with primary reflux. They were given continuous antibiotic prophylaxis and regularly followed up every 3 months. Relevant investigations were performed at every follow-up including monitoring of growth parameters. Outcome in terms of recurrent urinary tract infection (UTI) episodes, resolution of VUR, need for definitive surgery were analyzed. Results: Out of initial 48 patients enrolled in the study, three patients were lost for follow-up. Out of 45 patients (77 renal units), most of the patients had Grade III and IV reflux. Scarring was seen predominantly in Grade IV reflux (62.5%). At the end of 2 years, no units demonstrated Grade I reflux. Grade II reflux persisted in 16.67%. Grade III reflux persisted in 23.68%, while Grade IV reflux persisted in 62.5%. Most of the fresh UTI episodes occurred in Grade III and IV VUR patients. Fresh renal scars were seen mostly in Grade IV group. One patient underwent ureteric reimplantation due to fresh renal scar and persistent reflux. Conclusions: Conservative management of VUR with antibiotic prophylaxis appears to be a suitable option without adverse outcomes. In the current scenario, surgery has a minor role to play in the treatment of VUR..

Lentiviral Vectors Incorporating Ubiquitous Chromatin Opening Element Driving Canine CD18 Expression

Leukocyte adhesion deficiency type 1 (LAD1) in humans is caused due to mutations in the ITGB2 gene encoding the leukocyte CD18 subunit (b2 integrin). This results in defective leukocyte adhesion and migration leading to recurrent episodes of life-threatening bacterial infection. Canine leukocyte adhesion deficiency (CLAD) represents a disease-specific large animal model of LAD1 in which new therapeutic approaches could be tested. Our previous studies have demonstrated variable efficiency of CD18 expression under the control of several promoters. These include cellular promoters such as those of human elongation factor 1a (hEF1a): long (1169bp) and short (248bp) fragments, human phosphoglycerate kinase (hPGK), human CD11b and human CD18 genes. In addition, murine stem cell virus (MSCV) promoter has also been demonstrated to lead to very high levels of CD18 expression in CLAD CD34+ cells thereby reversing the CLAD phenotype in dogs previously treated with both foamy and lentiviral vectors. But, due to potential genotoxicity associated with the use of viral promoters, we continued our efforts in search of novel cellular promoters. One such promoter is the ubiquitous chromatin opening element (UCOE) from the human heterogeneous ribonucleoprotein A2/B1 and chromobox homolog 3 (HNRPA2B1-CBX3) loci. UCOE has been previously shown to display reproducible and stable transgene expression within the context of a self-inactivating (SIN) lentiviral vector in the absence of classical enhancer activity (Zhang et al., Blood 2007).It has also been shown to confer resistance to DNA methylation-mediated transgene silencing even upon integration into the heterochromatin regions of the host chromosome (Zhang et al., Mol Ther. 2010). Since the full-length element is about 2.6 kb, we cloned and tested different fragment lengths of the UCOE promoter in a SIN lentiviral vector (pCL20) in CLAD CD34+ cells in vitro. Efficiency of expression of CD18 obtained with the six promoter fragments of UCOE (in bp), namely U3'631, U3'1262, U3'652, U5'1357, U5'723 and U5'655 were compared to those obtained with an MSCV promoter. Functional viral titers were first determined using a human LAD EBV-transformed B-cell line that lacks endogenous human CD18. When comparable titers of each vector were used in an overnight transduction of CLAD CD34+ cells after a 24h cytokine prestimulation in vitro, the percentage of CD18+ cells 5 days after transduction were as follows: U3'631 - 8.49%, U3'1262 - 15.9%, U3'652 - 21.3% (tested at MOI 100), U5'1357 - 2.05% (tested at MOI 30), U5'723 - 2.44% (tested at MOI 20), U5'655 - 3.01% (tested at MOI 50) and MSCV - 35.3% (tested at MOI 100). The CD18 expression levels driven by some of these promoter fragments were comparable to those driven by cellular promoters mentioned previously. The UCOE is promising in that it could overcome possible gene silencing effects when used in vivo, unlike promoters such as EF1a and PGK which were largely subjected to post-transcriptional gene silencing with sub-therapeutic levels of CD18 as previously tested in the dog model. Hence, functional correction of the CD18 defect could be achieved with candidate UCOE-incorporating SIN lentiviral vector(s) when used in the treatment of CLAD dogs. DisclosuresNo relevant conflicts of interest to declare.

CKD and Risk for Hospitalization With Infection: The Atherosclerosis Risk in Communities (ARIC) Study

Individuals on dialysis therapy have a high risk for infection, but risk for infection in earlier stages of chronic kidney disease has not been comprehensively described. Observational cohort study. 9,697 participants (aged 53-75 years) in the Atherosclerosis Risk in Communities (ARIC) Study. Participants were followed up from 1996 to 1998 through2011. Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (ACR). Risk for hospitalization with infection and death during or within 30 days of hospitalization with infection. During follow-up (median, 13.6 years), there were 2,701 incident hospitalizations with infection (incidence rate, 23.6/1,000 person-years) and 523 infection-related deaths. In multivariable analysis, HRs of incident hospitalization with infection as compared to eGFRs≥90mL/min/1.73m2 were 2.55 (95% CI, 1.43-4.55), 1.48 (95% CI, 1.28-1.71), and 1.07 (95% CI, 0.98-1.16) for eGFRs of 15 to 29, 30 to 59, and 60 to 89mL/min/1.73m2, respectively. Corresponding HRs were 3.76 (95% CI, 1.48-9.58), 1.62 (95% CI, 1.20-2.19), and 0.99 (95% CI, 0.80-1.21) for infection-related death. Compared to ACRs<10mg/g, HRs of incident hospitalization with infection were 2.30 (95% CI, 1.81-2.91), 1.56 (95% CI, 1.36-1.78), and 1.34 (95% CI, 1.20-1.50) for ACRs≥300, 30 to 299, and 10 to 29mg/g, respectively. Corresponding HRs were 3.44 (95% CI, 2.28-5.19), 1.57 (95% CI, 1.18-2.09), and 1.39 (95% CI, 1.09-1.78) for infection-related death. Results were consistent when separately assessing risk for pneumonia, kidney and urinary tract infections, bloodstream infections, and cellulitis and when taking into account recurrent episodes of infection. Outcome ascertainment relied on diagnostic codes at time of discharge. Increasing provider awareness of chronic kidney disease as a risk factor for infection is needed to reduce infection-related morbidity and mortality.

Epidemiology of Initial and Recurrent Episodes of Infection in Left Ventricular Assist Device Recipients

Epidemiology of Initial and Recurrent Episodes of Infection in Left Ventricular Assist Device Recipients

Approach to Congenital Lobar Emphysema Presenting With Chronic Respiratory Failure Surgical vs Conservative Treatment

SESSION TITLE: Fellow Case Report Poster- Pediatrics SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: The rarity of reported cases of congenital lobar emphysema (CLE) makes management of a patient with failed conservative treatment a unique challenge CASE PRESENTATION: A two-week old previously healthy male initially presented with respiratory distress and central cyanosis. On admission, he developed supraventricular tachycardia. He reverted back to sinus rhythm after 2 doses of Adenosine. Respiratory viral panel and pertussis panel were negative. He remained mildly tachypneic and continued to require ½ LPM of oxygen. Initial CXR (Fig1) showed right upper lobe (RUL) opacity. His serum bicarbonate level continued to rise. Arterial blood gas revealed uncompensated respiratory acidosis. Flexible bronchoscopy showed left main stem bronchus and left upper lobe (LUL) malacia. Computed tomography (CT) of the chest (Fig2) revealed hyper-inflated LUL with compression atelectasis of the RUL. Other work ups include a normal brain MRI, normal alpha 1 anti-trypsin level and a negative sweat test. Surgery recommended conservative management at that time. The patient was re-admitted 45 days later due to acute respiratory failure secondary to human metapneumovirus bronchiolitis. Improvement in ventilation was noted while the patient was on mechanical ventilation; however, evidence of respiratory acidosis was seen after extubation. Upon follow in the Pulmonary and Surgery clinic, the patient continued to show evidence of respiratory acidosis, mild tachypnea, and sub-optimal weight gain. Due to failure of conservative management, a left upper lobectomy was performed. Microsopic findings from the surgical specimen showed uniform overdistension of the alveolar spaces. After the surgery, the patient clinically improved with resolution of tachypnea, normalization of respiratory acidosis and improved weight gain DISCUSSION: CLE is a rare congenital lung anomaly. Clinical presentation varies from acute respiratory distress to recurrent tachypnea. Chest radiograph, CT and bronchoscopy are usually sufficient for the diagnosis. Lobectomy is the universally accepted mode of treatment for CLE with severe symptoms. Some studies have reported successful conservative treatment in older patients presenting with milder symptoms, provided the patient is observed closely. During observation, if recurrent episodes of respiratory distress or recurrent infections occur, or in this case, chronic respiratory failure and poor weight, lobectomy should be performed CONCLUSIONS: To our knowledge, this is one of the few cases of CLE that failed conservative management. Surgical intervention should be considered in symptomatic CLE patients and those who failed conservative management. Reference #1: Chao M,et al.CLE:an Otolaryngologic Perspective.International Journal of Pediatric Otorhinolaryngology(2005)69,549-554 Reference #2: Ulku R,et al.CLE:Differential diagnsosis and therapeutic approach.Pediatrics International(2008)50,658-661 Reference #3: Mei-Zahav,et al Is CLE a surgical disease?Journal of Pediatric Surgery(2006)41,1058-1061 DISCLOSURE: The following authors have nothing to disclose: Wail Tfankji, Wendy Estrellado No Product/Research Disclosure Information

Prevalence of the Accessory Cardiac Bronchus on Multidetector Computed Tomography: Evaluation and Proposed Classification.

Accessory cardiac bronchus (ACB) is a very rare congenital anomaly and may cause some clinical complications, such as recurrent episodes of both infection and hemoptysis. The purpose of this study was to assess the multidetector computed tomography (MDCT) characteristics of ACB and to classify this anomaly according to the MDCT aspects. The routine thoracic CT scans from 5790 patients were evaluated retrospectively. The prevalence, location, length, diameter, division angle, distance from the carina, and the type of ACB were evaluated. A total of 12 ACBs were identified, with a prevalence of 0.2%. All ACBs originated from the intermediate bronchus. The median largest diameter of the ACBs was 7.75 mm (range: 5.8 to 10.30 mm), the median length was 12.1 mm (range: 8.6 to 35 mm), the median division angle was 61 degrees (range: 42 to 93 degrees), and the median distance from the carina was 16.95 mm (range: 5.7 to 22.20 mm). Six cases (50%) had a blind extremity (type 1: diverticulum or stump type), 3 cases (25%) had a mutiloculated cystic change at the end (type 2: cystic type), and 3 cases (25%) had a ventilated lobulus demarcated by an anomalous fissure (type 3: ventilated type). ACBs can be classified into 3 types according to their MDCT features. Recognition of ACB is important, as it is associated with clinical complications and is also salient in trauma cases.

Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections.

Neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM).We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software.Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell/macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ≥10 dilution (P < 0.05). Twenty-seven patients (60.0%) required long-term antimycobacterial therapy and had at least 1 episode of recurrent NTM disease. No mortality was related to dNTM infection.In Taiwan, nAIGAs are a recently recognized mechanism of dNTM infection. Long term of antibiotic treatment and adherence to medical advice are necessary to improve the clinical outcome of patients with nAIGAs.

Peritoneal dialysis: from bench to bedside and bedside to bench.

For patients with end-stage kidney disease unable to receive a kidney transplant, replacement of kidney function with dialysis is necessary to extend life. Peritoneal dialysis (PD) and hemodialysis (HD) are the two major forms of dialysis therapy. HD involves the passage of blood via an extracorporeal circuit whereby removal of small solutes, toxins, and water is achieved across a synthetic, semipermeable dialysis membrane. In contrast, in PD, the dialysis membrane is the highly vascularized internal lining of the peritoneal cavity. Intraperitoneal installation of hypertonic high glucose PD solution creates a transmembrane osmotic and diffusive gradient that facilitates water removal [ultrafiltration (UF)], convection, and diffusion of uremic toxins. Insight into the physiology of solute and water transport across the peritoneal membrane has been enhanced by the proposal of the ''three-pore model'' of peritoneal membrane transport. Transport characteristics and UF capacity of the peritoneal membrane vary among individuals, and deleterious changes in the membrane may ensue over time. The degree to which these changes are a direct consequence of the type and composition of currently available PD solutions, recurrent infectious episodes, genetic differences among individuals, or a combination thereof is the subject of intense study. Adverse consequences resulting from the systemic and local metabolic effects of intraperitoneal glucose exposure, infection of the PD fluid, PD catheter dysfunction, and patient burnout from self-care often limit the long-term success of the therapy. Research aimed at addressing these challenges will examine the use of more biocompatible PD solutions and strategies aimed at attenuating progressive peritoneal membrane injury.

Pharmacological Agents to Decrease New Episodes of Recurrent Lower Urinary Tract Infections in Postmenopausal Women. A Systematic Review.

The purpose of this systematic review was to evaluate and summarize pharmacological interventions evaluated in randomized clinical trials designed to prevent recurrent episodes of urinary tract infections (UTIs) in postmenopausal women. Excerpta Medica dataBASE, Pubmed, Medline, and Cochrane Library were accessed to search for nonexperimental drugs evaluated in randomized clinical trials published in peer reviewed journals from January 1, 1970, to August 1, 2015, to reduce the number of recurrent UTIs in postmenopausal women. A systematic search yielded 9 articles that met eligibility criteria. Five articles involved the use of systemic or vaginal estrogen therapy and the remainder used oral antibiotics, lactobacilli, or a combination of interventions. Antibiotics were the most efficacious therapy but with a higher incidence of systemic side effects. Oral lactobacillus was noninferior to sulfamethoxazole with trimethoprim with a safer profile in 1 small study. Vaginal estrogen appeared to be inferior to continuous oral antibiotic suppression; however, use of multiple formulations of both treatment options precludes meta-analysis. Oral estrogen use did not decrease UTI recurrence and resulted in local and systemic side effects in up to nearly 30% of the patients. This review supports the use of antibiotic suppression, vaginal estrogen, and oral lactobacillus for prevention of recurrent UTIs in postmenopausal women. However, the overall dearth of data suggests that this is an important but understudied population. Because the effectiveness and safety of available treatments are not well understood, they should be used with caution in older populations, pending further study.

Ultrastructural Variability of the Exosporium Layer of Clostridium difficile Spores.

The anaerobic sporeformer Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea in developed and developing countries. The metabolically dormant spore form is considered the transmission, infectious, and persistent morphotype, and the outermost exosporium layer is likely to play a major role in spore-host interactions during the first contact of C. difficile spores with the host and for spore persistence during recurrent episodes of infection. Although some studies on the biology of the exosporium have been conducted (J. Barra-Carrasco et al., J Bacteriol 195:3863-3875, 2013, http://dx.doi.org/10.1128/JB.00369-13; J. Phetcharaburanin et al., Mol Microbiol 92:1025-1038, 2014, http://dx.doi.org/10.1111/mmi.12611), there is a lack of information on the ultrastructural variability and stability of this layer. In this work, using transmission electron micrographs, we analyzed the variability of the spore's outermost layers in various strains and found distinctive variability in the ultrastructural morphotype of the exosporium within and between strains. Through transmission electron micrographs, we observed that although this layer was stable during spore purification, it was partially lost after 6 months of storage at room temperature. These observations were confirmed by indirect immunofluorescence microscopy, where a significant decrease in the levels of two exosporium markers, the N-terminal domain of BclA1 and CdeC, was observed. It is also noteworthy that the presence of the exosporium marker CdeC on spores obtained from C. difficile biofilms depended on the biofilm culture conditions and the strain used. Collectively, these results provide information on the heterogeneity and stability of the exosporium surface of C. difficile spores. These findings have direct implications and should be considered in the development of novel methods to diagnose and/or remove C. difficile spores by using exosporium proteins as targets.

Karyomegalic interstitial nephritis.

Karyomegalic interstitial nephritis is a singular type of progressive chronic interstitial nephritis. The pathogenesis of this disease is unknown. The present study reported the case of a 22-year-old man who presented with a long history of recurrent upper respiratory tract infection episodes secondary to bronchiectasis and with progressive renal failure. Renal biopsy revealed chronic tubulointerstitial nephritis and a surprisingly marked karyomegaly specifically of the tubular epithelium.

Immune Dysfunction in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a complex chronic disease. Chronic inflammation is the hallmark of COPD, involving the interplay of a wide variety of cells in the lung microenvironment. Cigarette smoke (CS) induces chronic lung inflammation and is considered a key etiological factor in the development and pathogenesis of COPD. Structural and inflammatory cells in the lung respond to CS exposure by releasing proinflammatory mediators that recruit additional inflammatory immune cells, which collectively contribute to the establishment of a chronic inflammatory microenvironment. Chronic inflammation contributes to lung damage, compromises innate and adaptive immune responses, and facilitates the recurrent episodes of respiratory infection that punctuate and further contribute to the pathological manifestations of the stable disease. A number of studies support the conclusion that immune dysfunction leads to exacerbations and disease severity in COPD. Our group has clearly demonstrated that CS exacerbates lung inflammation and compromises immunity to respiratory pathogens in a mouse model of COPD. We have also investigated the phenotype of immune cells in patients with COPD compared with healthy control subjects and found extensive immune dysfunction due to the presence and functional activity of T regulatory cells, CD4(+)PD-1(+) exhausted effector T cells and myeloid-derived suppressor cells. Manipulation of these immunosuppressive networks in COPD could provide a rational strategy to restore functional immune responses, reduce exacerbations, and improve lung function. In this review, we discuss the role of immune dysfunction in COPD that may contribute to recurrent respiratory infections and disease severity.

Effect of Transfer Factor on The Reduction of The Number of Episodes of Recurrent Infections In Adult And Pediatric Patients From A Multicentre Observational Study

Effect of Transfer Factor on The Reduction of The Number of Episodes of Recurrent Infections In Adult And Pediatric Patients From A Multicentre Observational Study

Perianal Fistula, Weight Loss, and Skin Rash: Good Job Making the Diagnosis

Gastroenterol Question: A 37-yearold man presented to his local hospital because of perianal discharge of 2 months duration, pelvic pain, and a 22-lb weight loss over the last 6 months. His medical history was notable for recurrent episodes of bronchitis and skin infections. The patient abused alcohol (8–10 beers per day). He did not take any medications or illicit drugs. Computed tomography (CT) of the abdomen revealed a pelvic abscess with fistulization into the perineum. He was started on intravenous fluids, antibiotics, and prednisolone and was then transferred to our hospital for further treatmentof suspected Crohn’s disease. At our hospital, physical examination revealed poor dentition, a large nasal bridge, and a left corneal ulcer. The skin was notable for an erythematous, fine, papular rash of the trunk, thighs and upper extremities (Figure A). Multiple small subcutaneous nodules, a subungueal abscess, and partial necrosis of the left toe were noted (Figure B). The patient also had scoliosis and a perianal fistulous opening (Figure C). A CT scan of the face and head revealed multiple small abscesses of the left orbit and double row dentition. Plain radiography of the left foot demonstrated left toe osteomyelitis. MRI of abdomen and pelvis showed a pelvic abscess with fistulization into the perineum (Figure D). Esophagogastroduodenoscopy, colonoscopy, double balloon enteroscopy, and capsule endoscopy were negative for inflammatory bowel disease. Laboratory studies revealed a white blood cell count within normal range, a decreased hemoglobin level of 8.4 g/dL and an increased platelet count of 504,000. The erythrocyte sedimentation rate was 100 mm/h and the Creactive protein was 47 mg/dL (normal, <5). The immunoglobulins IgA, IgM, and IgG yielded normal results but IgE was remarkably increased at 2520 IU/mL (normal, <100). The eosinophilic cationic protein was also significantly increased (130 mg/L; normal, <12).