Infections Of Upper Airways Research Articles

Nontypeable Haemophilus influenzae inhibits autolysis and fratricide of Streptococcus pneumoniae in vitro

Streptococcus pneumoniae (SP) and nontypeable Haemophilus influenzae (NTHi) are common commensals of the human airway and major bacterial pathogens of otitis media (OM) and other upper airway infections. The interaction between them may play an important role in the pathogenesis of polymicrobial infections. Although previous studies suggested NTHi could promote pneumococcal survival and biofilm formation, how NTHi affects pneumococcal activities has not been defined. Our data in the present studies indicated that the outcome of the interaction between SP and NTHi was in a cell-density-dependent manner and the enhancement of pneumococcal survival happened at the later stages of culturing. Using quantitative PCR, we found that the expression of pneumococcal genes regulating autolysis and fratricide, lytA and cbpD, were significantly down-regulated in co-culture with NTHi. We further observed that influence of NTHi was not on direct cell-to-cell contact, but that this contact may contribute to the interaction between these two microorganisms. These results suggest that pneumococcal survival and biofilm formation can be enhanced by down-regulating pneumococcal cell wall hydrolase production thereby inhibiting pneumococcal autolysis and fratricide in the presence of NTHi.

Ramsey Hunt syndrome — a case report

Case report: An 82-year-old woman with a history of hypertension and diabetes mellitus was presented to the Emergency Room (ER) because of left facial weakness of sudden onset and pain on the mastoid region. She had a history of a recent viral upper airway infection. On examination, she had a peripheral left facial nerve paralysis, with no other abnormalities. She was diagnosed with a Bell's Palsy and discharged from the ER with a prescription of prednisolon and recommendation for eye care measures.

Upper Airway Obstruction in Children: Prevalence, Diagnosis, Repercussions, and Comorbidities

Objectives: Investigate the prevalence, diagnosis, and repercussions of upper airway obstruction in children under 5 years-old and their impact in public health. Methods: A cross-sectional study was conducted with 197 children under 5, randomly selected from a population of 1500, from November 2011 to December 2012. Parents answered to anamnesis about respiratory problems, upper airway infections, perinatal history, and feeding habits. They answered validated questionnaires about sleep disordered breathing and allergies. All subjects underwent a physical examination, and those who complained of respiratory problems also had nasal fiberendoscopy. Results: 197 subjects (2.33 ± 1.09 y.o.), 107 boys. Prevalence of mouth breathing was 19.2%, nasal obstruction 18.2%, snoring 22.8%, rhinorrhea and sneezing 36.5%, and sleep disordered breathing (SDB) 7.1%. Diagnosis: adenoid enlargement (A) 8.6%, tonsil enlargement (T) 0.5%, tonsil and adenoid enlargement (T&A) 10.7%, rhinitis 21.9%, allergic rhinitis 7.6% (totalizing 49.6%). Fifty-five point seven percent of children were exclusively breast fed for at least 6 months, and no correlation was found with nasal obstruction. Sleep disordered breathing symptoms were found in 7.1 % and were associated only with T&A (64.2%). Children with upper airway obstruction were prone to upper airway infections and visits to the emergency room. Conclusions: Upper airway obstruction is prevalent in about 20% of children. Breast feeding was not correlated to mouth breathing. Rhinitis is a common diagnosis. T&A is associated with SDB and infections, consuming high resources. Doctors must investigate and refer young children with upper airway problems to treatment in order to minimize large consumption of health resources.

Functional maturation of nasal mucosa: role of secretory immunoglobulin A (SIgA)

Secretory IgA (SIgA) plays an important role in defending the mucous membranes of the upper respiratory airways from common infection. Studying and comparing the values and the daily variation of SIgA in nasal secretion could explain the largest number of upper respiratory infection, especially in children. Moreover, the ELISA dosage of SIgA in nasal secretion, sampled by cotton swabs positioned between septum and middle turbinate for 20 minutes every 4 hours 5 times in a day, can be easily performed and shows significant differences between the healthy child and the healthy adult. Nasal secretion SIgA mean value is lower in the healthy child than in the healthy adult. Circadian variation for healthy child showed the highest value at 7.00 a.m., while in adult the highest value was at 4.00 a.m. These knowledge on SIgA may help to explain the highest number of upper airway infection during childhood and clarify the physiological cycle of production. Thus, in performing a SIgA dosage the time of sample must be considered and preferably it should be made at a standardized time of the day.

Epidemiology of cough in relation to China

Cough is one of the most common complaints for which patients seek medical attention. Misdiagnosis and mistreatment of cough exist commonly in China. The prevalence of acute cough caused by upper airway infection fluctuates between 9% and 64% in the community, for chronic cough, the prevalence >10% in most surveys, ranging from 7.2%-33%. The common causes of chronic cough are upper airway cough syndrome (previously called as post nasal drip syndrome [PNDS]), cough variant asthma (CVA), gastroesophageal reflux related cough (GERD) and eosinophilic bronchitis (EB). There is a regional discrepancy regarding the prevalence of common causes of cough and distribution of gender among China, UK, USA, the most common cause of chronic cough in China are CVA, followed by UACS, EB and atopic cough (AC), the male is almost equal to female in numbers in China. The risk factors for cough includes cold air, smoking, environmental pollutants, noxious substances and allergens, and unreasonable diet habits.

The Emerging Role of the Bitter Taste Receptor T2R38 in Upper Respiratory Infection and Chronic Rhinosinusitis

Maintaining a clean upper respiratory tract requires efficient detection of pathogenic bacteria so that the airway mucosa can mount proper defenses to neutralize and clear the offending microbes. Bitter taste receptors (T2Rs) may play a critical role in this process. T2Rs were originally identified in taste cells of the tongue, where they protect against the ingestion of toxic plant and/or bacterial products. However, T2Rs are also expressed in extragustatory tissue including the airways. One specific T2R isoform, T2R38, was recently shown to be expressed in cilia of sinonasal epithelial cells, suggesting that respiratory cilia may function as a chemosensory organelle, possibly to detect bacterial presence in the airway. T2R38 is encoded by the TAS2R38 gene, which has several common genetic polymorphisms that result in altered receptor functionality. Genetic variation in T2R38 may thus contribute to individual differences in susceptibility to upper airway infection. This study provides an overview of our current knowledge of T2R38 function in sinonasal defense and the implications for patients with chronic rhinosinusitis (CRS). A literature review was performed of the current knowledge of the bitter taste receptor T2R38 in sinonasal physiology and CRS patient outcomes. Basic science research has indicated that the T2R38 receptor is activated by acyl-homoserine lactone (AHL) molecules secreted by gram-negative bacteria, including Pseudomonas aeruginosa. In sinonasal epithelial cells T2R38 stimulates an increase in nitric oxide production that increases mucociliary clearance and directly kills bacteria. Recent clinical studies have also found clinical correlations of TAS2R38 genotype with susceptibility to gram-negative upper respiratory infection as well as necessity for surgical intervention in CRS management. T2R38 appears to be an important mediator of sinonasal epithelial defense, but further study is needed to more clearly determine how TAS2R38 genotype affects patient outcomes in CRS and other upper airway diseases.

SP0032 Mucopolysaccharidoses - what should the rheumatologist know?

Mucopolysaccharidosis (MPS) are lysosomal disorders belonging to the inborn errors of metabolism. MPS are caused by a deficiency in one of the enzymes responsible for the degradation of glycosaminoglycans (GAGs),...

Cdc42 Promotes Host Defenses against Fatal Infection

The small Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, invasion, migration, differentiation, and morphogenesis. As the role of Cdc42-dependent signaling in fibroblasts in vivo is unknown, we attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections that were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific Cre mouse, we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate immunity.

Expanding the BP1-BP2 15q11.2 Microdeletion Phenotype: Tracheoesophageal Fistula and Congenital Cataracts

The proximal q arm of chromosome 15 contains breakpoint regions BP1–BP5 with the classic deletion of BP1–BP3 best known to be associated with Prader-Willi and Angelman syndromes. The region is approximately 500 kb and microdeletions within the BP1-BP2 region have been reported in patients with developmental delay, behavioral abnormalities, and motor apraxia as well as dysmorphic features including hypertelorism, cleft or narrow palate, ear abnormalities, and recurrent upper airway infections. We report two patients with unique, never-before-reported 15q11.2 BP1-2 microdeletion syndrome findings, one with proximal esophageal atresia and distal tracheoesophageal fistula (type C) and one with congenital cataracts. Cataracts have been described in Prader-Willi syndrome but we could not find any description of cataracts in Angelman syndrome. Esophageal atresia and tracheoesophageal fistula have not been reported to our knowledge in either syndrome. A chance exists that both cases are sporadic birth defects; however, the findings of the concomitant microdeletion cannot be overlooked as a possible cause. Based on our review of the literature and the presentation of our patients, we recommend that esophageal atresia and distal tracheoesophageal fistula as well as congenital cataracts be included in the phenotypic spectrum of 15q11.2 BP1-2 microdeletion syndrome.

Group A Streptococcal Meningitis in a Patient with Palmoplantar Pustulosis

A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality.

Functional maturation of nasal mucosa: role of secretory immunoglobulin A (SIgA)

Secretory IgA (SIgA) plays an important role in defending the mucous membranes of the upper respiratory airways from common infection. Studying and comparing the values and the daily variation of SIgA in nasal secretion could explain the largest number of upper respiratory infection, especially in children.Moreover, the ELISA dosage of SIgA in nasal secretion, sampled by cotton swabs positioned between septum and middle turbinate for 20 minutes every 4 hours 5 times in a day, can be easily performed and shows significant differences between the healthy child and the healthy adult.Nasal secretion SIgA mean value is lower in the healthy child than in the healthy adult. Circadian variation for healthy child showed the highest value at 7.00 a.m., while in adult the highest value was at 4.00 a.m.These knowledge on SIgA may help to explain the highest number of upper airway infection during childhood and clarify the physiological cycle of production. Thus, in performing a SIgA dosage the time of sample must be considered and preferably it should be made at a standardized time of the day.

Tonsilloplasty versus tonsillectomy in children with sleep‐disordered breathing: Short‐ and long‐term outcomes

Adenoidectomy and tonsillectomy (TE) is the standard treatment for obstructive sleep-disordered breathing (SDB) in children with adenotonsillar hypertrophy. Tonsilloplasty (TP) is a new surgical technique that includes partial TE. The purpose of this study was to assess the short- and long-term outcomes of TP compared to TE. A comparison study. Children with SDB and tonsillar hypertrophy underwent TP or TE. The two groups were compared regarding immediate postoperative course and long-term effects. Fifty-one children (age, 6.3 ± 2.5 years) underwent TE, and 50 children (age, 5.9 ± 2.1 years) had TP. The TP group had significantly less intraoperative bleeding compared to the TE group (25.6 ± 8.2 vs. 38.3 ± 12.3 mL, P < .001). Subjects with TP were pain free earlier than children with TE (4.5 ± 0.4 vs. 7.7 ± 0.4 days, P < .001) and returned to a normal diet sooner (3.8 ± 0.2 vs. 7.1 ± 0.3 days, P < .001). By the 3rd to 4th postoperative night, upper airway obstruction was relieved in all participants. Six years postoperatively, 48 of 51 children in the TE group and 43 of 50 children in the TP group participated in a telephone survey. No significant differences were found between the two groups regarding the frequency of recurrent snoring (30.2% in TP vs. 25% in TE), apneas (4.7% vs. 0%), and upper airway infections per year (P > .05). TP is an alternative surgical method for treatment of SDB related to tonsillar hypertrophy with favorable postoperative course and comparable long-term results. 2c.

Perfil de prescritores e prescrição de antimicrobianos nas infecções das vias aéreas superiores em Pediatria

OBJETIVO: Traçar um perfil dos médicos que atendem crianças nos sistemas público (Sistema Único de Saúde) e privado de saúde e verificar como são prescritos antimicrobianos nas infecções das vias aéreas superiores. MÉTODOS: Médicos de algumas cidades do interior do Estado de São Paulo receberam via correio ou nas Unidades Básicas de Saúde uma carta explicativa sobre a pesquisa e o questionário, com perguntas sobre: tempo de graduação, residência médica, carga horária e local de trabalho, forma de atualização, fatores que consideram ao prescrever antimicrobianos e casos clínicos sobre as infecções das vias aéreas superiores. Os dados pessoais dos médicos foram relacionados com as respostas aos casos clínicos. Para análise estatística, foram aplicados os testes Z e de Tukey-Kramer, sendo p&lt;0,05 significante. RESULTADOS: A amostra foi composta por 170 prescritores: 86,5% possuíam residência em Pediatria, 75% trabalhavam no Sistema Único de Saúde e 71% tinham carga horária superior a 40 horas semanais. Os formados há menos de dez anos valorizaram mais os laboratórios farmacêuticos como forma de atualização do que os graduados há mais de 30 anos; 33% dos médicos do Sistema Único de Saúde atendem mais de cinco pacientes por hora. A média de acerto nos casos clínicos foi de 87%. O uso das entidades médicas como forma de atualização foi associado a respostas corretas, enquanto o uso de materiais de laboratório estava ligado a respostas incorretas (p&lt;0,05). Houve clara tendência de diminuição dos acertos conforme o número de pacientes atendidos por hora aumentava. CONCLUSÕES: Educação adequada sobre o tema e melhora nas condições de trabalho podem ser eficientes para reduzir a prescrição de antibióticos para infecções das vias aéreas superiores em crianças.

Neuroborreliosis Presenting as Acute Disseminated Encephalomyelitis

We report a case of a 5-year-old boy with acute disseminated encephalomyelitis as the initial presentation of neuroborreliosis. Parents report an upper-airway infection a few days before the development of acute encephalopathy, mild facial palsy, and seizures. The patient needed mechanical ventilation for 10 days, and after extubation, he presented hypotonia, ataxia, dysarthria, as well as weak gag and cough reflexes. Brain magnetic resonance imaging showed hyperintense lesions on T2- and fluid-attenuated inversion recovery sequences on the right subcortical occipital and parietal region, left posterior arm of the internal capsule, and in the medulla oblongata. Borrelia burgdorferi was identified in the plasma and cerebrospinal fluid by polymerase chain reaction and in the plasma by Western blotting. He was treated with ceftriaxone, methylprednisolone, and human immunoglobulin. Recovery was partial.

Sleepiness that cannot be overcome: Narcolepsy and cataplexy

Narcolepsy-cataplexy syndrome is characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. It is strongly associated with the genetic marker, human leucocyte antigen (HLA) DQB1*06:02. A deficit in the endogenous hypocretin/orexin system due to neuronal degeneration in the lateral hypothalamus, induced by an autoimmune-mediated process, is the primary pathophysiology associated with the human disease. The important finding of an association with hypocretin genes in animal models of narcolepsy has led to the establishment of cerebrospinal fluid hypocretin measurements as a new diagnostic test for human narcolepsy. This is a fascinating story of translation of basic science research into clinical practice in sleep medicine during the past decade. Recent advances have shed light on the associations between respiratory medicine and narcolepsy-cataplexy research. The first is that upper airway infections, including H1N1 and/or streptococcal infections, may initiate or reactivate an immune response that leads to loss of hypocretin-secreting cells and narcolepsy in genetically susceptible individuals. The second is that an increased incidence of sleep disordered breathing among narcoleptic subjects may relate to the impairment of central control of breathing, linked to hypocretin deficiency or carriage of HLADQB1*06:02, in animals and human subjects with narcolepsy, respectively, indicating neural dysfunction in an area where respiratory and sleep-wake systems are closely interrelated.

Diversity of mucosal immune responses in upper respiratory airways and the suitability of mucosal vaccines

SummaryMucosal vaccines are considered to be a promising strategy for preventing upper airway infections. As immunization routes to induce mucosal immune responses, oral, intranasal and sublingual immunizations have been proposed for clinical application. Recently, it was reported that transcutaneous immunization (TC) is also capable of inducing mucosal as well as systemic immune responses. However, it remains unclear which route is most effective for inducing mucosal immune responses in upper respiratory airways. In this study, the mucosal immune responses against phosphorylcholine (PC), a structural component of a wide variety of Gram‐positive and ‐negative bacteria, were investigated after intranasal, sublingual, or TC. Female BALB/c mice were immunized intranasally, sublingually, or transcutaneously with PC and cholera toxin. For the TC, the dorsal region was shaved and a cotton patch soaked with the antigen was attached. Nasal wash, saliva and serum samples were collected at 7 days after the final immunization, and examined for their PC‐specific antibody activities using ELISA. Phosphorylcholine‐specific antibodies in serum and PC‐specific IgA in nasal washes and saliva were detected in mice after intranasal and sublingual immunization with PC. Although salivary IgA was higher following intranasal immunization, nasal wash IgA was significantly higher after sublingual immunization. Furthermore, significantly increased IgA in vaginal washes and remarkably decreased serum IgE production were observed after sublingual immunization. TC increased PC‐specific IgA in faecal samples, but not in saliva. The PC antigen can induce mucosal as well as systemic immune responses when administered via intranasal, sublingual and transcutaneous routes. Sublingual immunization is superior to intranasal immunization in terms of safety for inducing mucosal immune responses. Although TC might be an alternative way to induce mucosal immune responses, further investigation is needed for its application as a vaccine route to prevent upper airway infection.

1833 Acute Necrotizing Encephalopathy of Childhood Associated with Influenza A

BackgroundEach year many children suffer from respiratory infections caused by Influenza A virus, but only a limited number experiences severe complications. One of these serious complications is an acute necrotizing...

De novo 13q12.3–q14.11 deletion involving BRCA2 gene in a patient with developmental delay, elevated IgM levels, transient ataxia, and cerebellar hypoplasia, mimicking an A‐T like phenotype

We report on a child with a de novo deletion of approximately 12 Mb detected through array comparative genomic hybridization (CGH). The deletion involved chromosome bands 13q12.3-13q14.11 and determined the loss of ≥50 genes. A second deletion on chromosome 12p11.3p11.22 of 43-167 kb, including about 12 genes, was unlikely of clinical relevance because inherited from the asymptomatic father. The child had developmental delay, dysmorphisms, and many features reminiscent of ataxia-telangiectasia (A-T), as cerebellar ataxia, oculocutaneus telangiectasia, and recurrent upper airway infections. Atraumatic fractures of the metatarsus were noted. Moreover, this is a rare case of 13q deletion syndrome associated with peripheral blood white cells radiosensitivity to bleomycin, reminiscent of what previously reported on X-ray hypersensitivity of fibroblasts from patients with alterations of this chromosome. The immunological evaluation revealed increased IgM serum levels and a low proliferative response to mitogens, PHA, and CD3 cross-linking (CD3 XL). After 12 years of age only a mild dysmetria persisted, while the proliferative response to mitogens became normal by 9 years of age.

Granulomatosis with polyangiitis involves sustained mucosal inflammation that is rich in B-cell survival factors and autoantigen

Granulomatosis with polyangiitis (GPA) is a rare chronic autoimmune disease that may be triggered by upper airway infection. ANCAs specific for PR3 that is expressed by activated neutrophils and macrophages are associated with GPA. Our aim was to investigate regional immune mechanisms that might induce or support the autoimmune response in GPA. Biopsy samples from 77 patients including 8 with GPA were studied by immunohistochemistry. B-cell homing subsets in blood samples from 16 patients with GPA and 11 healthy controls were studied by FACS. The distribution of B-cell clones was searched in paired biopsies and blood samples from one patient by analysing immunoglobulin heavy chain gene (IGH) junctional sequences. Activated B cells were located alongside PR3-expressing cells and B-cell survival factors BAFF and APRIL in mucosa from patients with GPA. We detected APRIL production by the granulomas and giant cells. B cells were proliferating in all cases and persistent for 5 years in biopsies obtained from one patient. However, there was no evidence of B-cell clones from the mucosal biopsies circulating in peripheral blood in GPA or any numerical or proportional change in B-cell subsets expressing markers of regional homing in blood in GPA. Our study illustrates chronically activated B cells alongside autoantigens and B-cell survival factors in the mucosa in GPA.

Periodic Lateralized Epileptiform Discharges (PLEDs) and pneumococcal meningoencephalitis

Pneumococcal meningoencephalitis (PME) is a life-threatening condition of the central nervous system (CNS), and is often the result of a complicated upper airway infection. Periodic Lateralized Epileptiform Discharges (PLEDs) are a typical electroencephalographic (EEG) pattern found in some acutely acquired brain insults. Within the pediatric population they are frequently seen in association with herpetic encephalitis, a CNS infection with a high morbidity and mortality rate. We report the case of a 3-year-old girl with a bilateral ear infection who developed convulsions and coma. She had early PLEDs lateralized to the right on the EEG and microbiological criteria for Streptococcus pneumoniae infection. Concomitant herpetic encephalitis was ruled out. Intensive antibiotic and antiepileptic treatment resulted in a remarkable improvement, with the patient being able to resume her normal activities within months. To our knowledge, the association of PME and PLEDs has not been previously described in children. On the other hand, EEG has scarcely been used in the management of acute CNS infections. Hence, non-herpetic CNS encephalitis with potentially more favorable outcomes ought to be considered in the differential diagnosis of PLEDs. Continuous EEG monitoring should be considered in children with CNS infections presenting with altered sensorium, independent of the presence of seizures.