Recurrent Lower Respiratory Tract Research Articles

Lower respiratory tract infections among newly diagnosed sleep apnea patients

BackgroundSleep apnea is associated with chronic comorbidities and acute complications. Existing data suggest that sleep apnea may predispose to an increased risk and severity of respiratory tract infections.MethodsWe investigated the incidence of lower respiratory tract infections in the first and second year before and after diagnosis of sleep apnea in a Finnish nationwide, population-based, retrospective case–control study based on linking data from the national health care registers for primary and secondary care from 2015–2019. Controls were matched for age, sex, hospital district, and multimorbidity status. We furthermore analysed the independent effect of comorbidities and other patient characteristics on the risk of lower respiratory tract infections, and their recurrence.ResultsSleep apnea patients had a higher incidence of lower respiratory tract infections than their matched controls within one year before (hazard ratio 1.35, 95% confidence interval 1.16–1.57) and one year after (hazard ratio1.39, 95% confidence interval1.22–1.58) diagnosis of sleep apnea. However, we found no difference in the incidence of lower respiratory tract infections within the second year before or after diagnosis of sleep apnea in comparison with matched controls. In sleep apnea, history of lower respiratory tract infection prior to sleep apnea, multimorbidity, COPD, asthma, and age greater than 65 years increased the risk of incident and recurrent lower respiratory tract infections.ConclusionsSleep apnea patients are at increased risk of being diagnosed with a lower respiratory tract infection within but not beyond one year before and after diagnosis of sleep apnea. Among sleep apnea patients, chronic comorbidities had a significant impact on the risk of lower respiratory tract infections and their recurrence.

Primary ciliary dyskinesia in children

Primary ciliary dyskinesia is characterized by impaired mucociliary clearance and contributes to the recurrence of recurrent and chronic upper and lower respiratory tract infections. In this paper we elucidated a clinical case confirmed in the Pneumology Clinic of the Institute of Mother and Child, where he was investigated by ECG, pulmonary Rg, pulmonary CT, saccharin test. Morbid history of persistent wet cough, mucopurulent sputum, nasal voice, difficult nasal breathing. Radiography of the paranasal sinuses showed signs of pansinusitis. At pulmonary CT, there were characteristic signs of chronic broncho-pulmonary processes - varicose and sac-shaped bronchiectasis, pleuro-pulmonary adhesions, fibro-atelectatic areas in various segments. Spirometry – moderate and severe restrictive and obstructive disorders.

Does the Hyper IgM Phenotype Affect Prognosis in Ataxia Telangiectasia?

Objective: To evaluate the characteristics of the patients who were followed-up with the diagnosis of ataxia telangiectasia (AT) and to assess the relationship between the hyper IgM (HIGM) phenotype and their prognosis. Materials and Methods: From 2007 to 2019, the study included 68 patients aged 3-35 years who were followed-up with the diagnosis of AT. We retrospectively evaluated the clinical and immunological characteristics and follow-up results. Results: There were 36 girls and 32 boys with a median follow-up of 10 years (1-12 years). The most common complaints upon admission were unsteady walk in 87%, infection in 6%, presence of a family history in 6%, and intracranial mass in 1%. The marriage was consanguineous in 85% of the parents. Ataxia was seen in 100% of the patients, telangiectasia in 97%, and immune deficiency in 88%. Bronchiectasis was observed in 23.5% of the patients, chronic diarrhea in 19%, lymphoproliferation in 15%, malignancy in 10%, autoimmunity in 10%, liver failure in 6%, and granulomatous skin lesions in 6%. Thirteen patients (19%) died during follow-up. The HIGM phenotype was identified in 31% of the patients. Recurrent upper and lower respiratory tract infections (p=0.004 and p<0.0001, respectively), liver failure (p=0.005), and autoimmune diseases (p=0.023) were significantly higher in the HIGM (+) group than the HIGM (-) group. Life expectancy was shorter in the HIGM (+) group with 14 ± 0.73 years (CI 95% 12.55-15.44) compared to the HIGM (-) group with 18 ± 1.64 years (CI 95% 14.77-21.22) (p=0.054). Conclusion: During the early childhood period and before the characteristic findings of AT develop, the patients might present at a hospital with infections, autoimmunity, lymphoproliferation, or malignancy. Physical examination, high alpha-fetoprotein (AFP) levels and immunological testing provide important data for the correct diagnosis. The HIGM phenotype aggravates the clinical course of the disease resulting in fatalities at an earlier age and at a higher rate.

Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency

Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny.

Common variable immunodeficiency: An uncommon cause of bronchiectasis, granulomatous disease, chronic liver disease, and enteropathy – Case report and review of literature

Common variable immune deficiency (CVID) is a primary immunodeficiency syndrome, characterized by a defective B cell function. Although there is no age or gender predilection, it is usually diagnosed between the second and fourth decades of life. The clinical features are diverse and include recurrent infections and autoimmune and granulomatous diseases, along with an increased risk of malignancies. Respiratory involvement occurs commonly in the form of recurrent upper and lower respiratory tract infections (LRTI), at times resulting in bronchiectasis. Gastrointestinal involvement may manifest either in the form of an infectious diarrhea due to parasites such as Giardia lamblia and bacteria such as Campylobacter jejuni, or as a noninfectious enteropathy resembling coeliac disease or inflammatory bowel disease. Some patients develop a granulomatous disease manifesting with noncaseating granulomas, especially of lymph nodes, skin, lung, spleen, and liver. Nearly 20%–25% of cases develop autoimmune complications such as autoimmune hemolytic anemia and immune thrombocytopenia. Hepatic involvement can occur in the form of abnormal biochemistry, nodular degenerative hyperplasia, and cirrhosis of liver. Treatment of infection, and replacement of immunoglobulins, remains the mainstay of management of CVID. Herein, we describe the case of a 48-year-old female, who initially presented to our hospital with recurrent bouts of upper and LRTI, along with small-bowel diarrhea, and progressively developed generalized lymphadenopathy and ascites, before being finally diagnosed by the rheumatologist, as a case of CVID, with associated CVID-related enteropathy, granulomatous disease, and chronic liver disease. She was managed with immunoglobulin replacement therapy, along with hydroxychloroquine and steroids with good response.

An X-Linked Hyper-IgM Patient Followed Successfully for 23 Years without Hematopoietic Stem Cell Transplantation

When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patient regarding hematopoietic stem cell transplantation or intravenous immunoglobulin replacement therapy with P. jiroveci prophylaxis. A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media. His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping and inadequate specific antibody responses. He was diagnosed as common variable immunodeficiency and began to receive intravenous immunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremely well and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand his molecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found in CD40LG gene. The mother was heterozygous carrier for this mutation and his sister did not have any mutation. Flow cytometric analysis for CD40LG expression on activated T cells showed highly decreased, but not absent, CD40LG expression. In conclusion, diagnostic delay is a clinical problem for patients with CD40LG deficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemic patients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined for CD40LG expression on activated T lymphocytes. Secondly, type of CD40LG mutations leads to enormous interpatient variations regarding serum IgM levels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or without hematopoietic stem cell therapy.

A Randomized, Double-Blind Placebo-Controlled, Multi-Centric Clinical Trial of Ultra-diluted Mycobacterium tuberculosis Nosode (Emtact 30C) in the Management of Recurrent Upper and Lower Respiratory Tract Affections

A Randomized, Double-Blind Placebo-Controlled, Multi-Centric Clinical Trial of Ultra-diluted Mycobacterium tuberculosis Nosode (Emtact 30C) in the Management of Recurrent Upper and Lower Respiratory Tract Affections

The involvement of musculoskeletal system and its influence on postural stability in children and young adults with cystic fibrosis

BackgroundCystic fibrosis (CF) affects the musculoskeletal system via a multifactorial pathway that includes vitamin D deficiency and involvement of respiratory muscles such as intercostals due to recurrent upper and lower respiratory tract infections. Eventual result is the deterioration of musculoskeletal health and posture in CF patients. Postural stability is directly affected by posture and can be compromised in every musculoskeletal problem. The aim of this study is to evaluate musculoskeletal system and postural stability in patients with CF.MethodsPatients with CF over six years of age and age and sex-matched control groups were included in the study. Cobb angle and thoracic kyphosis angles were measured on the spine radiographs. Both patients and control group were examined with pediatric gait, arms, legs and spine scale (pGALS). They also were evaluated with a NeuroCom Balance Master for their postural stability.ResultsFifty-one patients with CF and 94 healthy controls participated in the study. In results of the pGALS examination, CF group had significantly more pathological findings than the control group in lower extremity appearance and movement (p = 0.006 and p = 0.01) and spine appearance and movement (p = 0.001 and p = 0.022) domains. The tandem walking speed was significantly higher in controls with a mean of 24.45 ± 7.79 while it was 20.47 ± 6.95 in the CF group (p = 0.03). Various limits of stability parameters also showed significant differences. Medium correlations were found between musculoskeletal examination and postural stability parameters.ConclusionIn patients with CF, a systematic but simple musculoskeletal examination can detect pathologies, which are more frequent than the normal population. These pathologies show a medium correlation with the involvement of postural stability.

Good syndrome associated with pure red cell aplasia in a patient with a history of thymoma: A case report and literature review

Abstract Objectives Good syndrome is a rare condition in which a thymoma is associated with hypogammaglobulinemia. It is also characterized by low or absent B-cells, CD4+ T-cell lymphopenia, inverted CD4/CD8+ T-cell relation, and repeated bacterial, viral, and fungal infections, as well as with various autoimmune disorders. Case report We report the case of a 62-year-old female patient who after resection of a thymoma developed constipation and recurrent lower respiratory and urinary tract infections. She underwent left hemicolectomy as well as symptomatic and antibiotic treatment. Two years later the patient develops refractory anemia; a bone marrow biopsy shows hypo-cellularity and no red cell precursors with negative CD 71 staining. The diagnosis of pure red cell precursor aplasia (PRCA) is made. Recurrent bacterial infections of the respiratory and urinary tracts continue, and therefore treatment with G and A immunoglobulins starts. Finally, the absence of B lymphocytes and inversion of CD4/CD8 relation confirms the diagnosis of Good syndrome associated with PRCA. Discussion The discovery of Good Syndrome and PRCA after the resection of a thymoma, as seen in the current case, is very unusual. This case illustrates both the rareness presentation of Good syndrome with PRCA and the persistent infections seen in these patients. Early recognition of these entities results in lower mortality and morbidity.

Analysis of the clinical characteristics of Kartagener syndrome in Chinese and foreign children

To analyze the clinical characteristic of Kartagener syndrome in Chinese and foreign children. Four cases of Kartagener syndrome diagnosed in our hospital were analyzed with literature review. The differences between Chinese and foreign children in clinical manifestations and diagnosis were compared. All of the cases had the following clinical manifestations: recurrent productive cough, nasosinusitis, dextrocardia, total situs inversus and bronchiectasia. Situs inversus of the airway structure was visible under the bronchoscope, and electron microscopy of the respiratory mucosa showed an abnormal ciliary ultrastructure. By using "Kartagener syndrome" and "child" as the key words, reports on 55 Chinese cases and 61 foreign cases in children were retrieved from CNKI and PubMed databases. The average age of diagnosis was 9.16 ± 3.67 years in China, which was significantly later than 7.07 ± 4.92 years in foreign countries (t=2.642, P<0.01). The main clinical manifestations were recurrent productive cough, nasosinusitis or rhinopolyp, recurrent pulmonary infection, recurrent wheezing and otitis media. Sinus imaging showed maxillary sinusitis. Dextrocardia, total situs inversus and bronchiectasia were found on thoracic and abdominal CT. The ciliary ultrastructural analysis showed shorter and missing dynein arm (6/6 cases in China and 25/27 cases in foreign) . The clinical manifestations are recurrent upper and lower respiratory tract infection combined with dextrocardia or other situs inversus in both China and other countries. The diagnosis abroad relied more on abnormal ciliary ultrastructure observed under electron microscopy, but in China mainly relied on its typical clinical manifestations.

Home oxygen for children with neurodisability—do we know why we are using it?

Aims To review the use and monitoring of home oxygen in children with disability for palliative and non-palliative care purposes. Method The caseload of a team of community nurses serving children with severe disability was reviewed to establish numbers and details of children on home oxygen. The monitoring arrangements according to community nurses were compared with parents9 perception of monitoring and parameters ascertained by phone call. Results The caseload was 77 children with neurodisability aged 3 months–18.5 years. 15 children (eight females) with age range 15 months–17 years (mean 8 years) had been receiving home oxygen in the past 12 months. Two children had neurodegenerative conditions, 13 had severe static neurodisability. Five children were receiving oxygen for symptomatic relief as part of palliative care: four continuously and one intermittently. Three other children were receiving continuous oxygen: one for chronic neonatal lung disease and two for upper airway problems causing recurrent cyanotic episodes. Seven others were receiving intermittent oxygen: five for treatment of hypoxia during recurrent acute lower respiratory tract infections, one for respiratory depression associated with seizures and one for potential emergencies occurring during school transport. All nursing records described the oxygen treatment in detail with appropriate monitoring arrangements. However, in four cases (25%) the indications for oxygen and the monitoring actually being used were very different according to parents. Conclusions There were several discrepancies between the reasons for home oxygen and the target oxygen saturations according to community nurses9 notes and parents9 understanding. Monitoring arrangements were appropriate. No children had satisfactory written care plans and it was not recorded whether potential hazards of home oxygen had been discussed. Oxygen is a prescription treatment with some significant safety implications. Indications for its use in the palliative or non-palliative setting should be clear. Following this audit a communication sheet was devised, including indications for oxygen therapy, monitoring arrangements, information and support given.

Helicobacter pylori infection and reflux esophagitis in children with chronic asthma.

Reflux esophagitis is uncommon in countries in which most people are colonized by H. pylori infection and is extremely rare in persons with reflux esophagitis, although esophagitis is detected in almost 50% of children with recurrent lower respiratory tract symptoms. Failure to acquire H. pylori can enhance esophagitis risk in children with chronic asthma. Forty-two pediatric out-patients with chronic asthma (mean age 13.2 +/- 1.18 years, range 12-15 years, 23 boys and 19 girls) were included in the study. They had undergone endoscopy with gastric and esophageal biopsies for upper dyspeptic complaints. H. pylori positivity was confirmed by positive Giemsa staining. Esophagitis was diagnosed by standard histologic procedure (presence of intraepithelial leukocytes or basal cell hyperplasia). H. pylori colonization was detected histologically in 22 of 42 patients (52.4%) enrolled in the study. Histology demonstrated that in asthmatic children with evidence of H. pylori infection esophagitis was a dramatically rare finding than in the patients without the infection (P < 0.001). It was an unexpected finding, that lung function parameters (FEF50, FEF75) were significantly lower in asthmatics infected with H. pylori (P < 0.05). The present findings suggest inverse association between esophagitis and H. pylori in course of asthma in pediatric patients.