Exhausted and Apoptotic BALF T Cells in Proinflammatory Airway Milieu at Acute Phase of Severe Mycoplasma Pneumoniae Pneumonia in Children

Severe mycoplasma pneumoniae pneumonia (MPP) in children presents with serious clinical complications. Without proper and prompt intervention, it could lead to deadly consequences. Dynamics of the inflammatory airway milieu and activation status of immune cells were believed to be the hallmark of the pathogenesis and progress of the disease. In this study, by employing the T-cell sorting and mRNA microarray, we were able to define the main feature of the chemokine/cytokine expression and the unique characteristics of T cells in the bronchoalveolar lavage fluid (BALF) from severe MPP patients at acute phase. Our study for the first time delineated the molecular changes in isolated BALF T cells in severe MPP children with respect to the cytokine/chemokine expression, cell activation, exhaustion, and apoptosis. By comparing the BALF aqueous expression of cytokines/chemokines with that in sorted T cells, our data give a preliminary clue capable of finishing out the possible cell source of the proinflammatory cytokines/chemokines from the BALF mixture. Meanwhile, our data provide a distinctively pellucid expression profile particularly belonging to the isolated BALF T cells demonstrating that in the inflammatory airway, overactivated T cells were exhausted and on the verge of apoptotic progress.

Clinical Characteristics of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Korean Children: A Multicenter Retrospective Study

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Association of Mycoplasma pneumoniae coinfection with adenovirus pneumonia severity in children

Between the winter of 2018 and the end of 2019, there has been an epidemic of adenovirus infection in southern China, including Zhejiang Province. The number of children suffering from adenovirus pneumonia (AP) has significantly increased. AP can be accompanied by Mycoplasma pneumoniae in children. This study aimed to investigate the association of M. pneumoniae and identify the risk factors for coinfection on hospitalized patients with AP. The patients were classified into two groups by etiologic analysis (single AP and AP with M. pneumoniae coinfection groups). The clinical manifestations, clinical medication, and laboratory and imaging findings of the two groups were compared and analyzed. The coinfection group (n = 125) had a significantly longer duration of fever than the single AP group (n = 171; P = 0.03). Shortness of breath (P = 0.023) and pulmonary imaging findings, such as pulmonary consolidation, atelectasis, pleural effusion, and multilobe lesions (P < 0.05), were more common in the coinfection group. The patients with coinfection had more severe symptoms, significantly longer hospitalization time and an increased proportion of using glucocorticoids and/or immunoglobulin needing oxygen inhalation (P < 0.05). The incidence of AP with M. pneumoniae coinfection is high. The prolonged fever duration and pulmonary imaging findings could be used as prediction factors to predict M. pneumoniae coinfection in children with AP. Patients with AP coinfected with MP may easily develop severe illness. Hence, a reasonable change in the treatment is necessary.

The Incidence and Risk Factors of Extrapulmonary Manifestations in Mycoplasma Pneumoniae Pneumonia

Background: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community acquired pneumonia (CAP) in children and it is known to be associated with extrapulmonary manifestations (EPM). The incidence and risk factors of EPM in children are not known.Methods: This is a retrospective study involving 65,243 pediatric CAP patients between 2010 and 2015 at 23 nationwide hospitals was conducted in South Korea. The medical records were reviewed to collect the information regarding the clinical characteristics, radiological results, and laboratory findings. In total, 9,190 children with MP were identified and included in the analysis. Logistic regression with multivariable analysis was performed to evaluate the risk factors associated with EPM in MP.Results: The mean age of the enrolled patients with MP was 64.3±39.8 months, and the proportion of male patients was 49.5%. The incidence of EPM was 23.9% and included elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurologic manifestation (0.4%), hematologic manifestation (0.2%) and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations were significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR] 3.623, 95% confidence intervals [CI] 1.933-6.790) and atopic sensitization (aOR 2.973, 95% CI 1.615-5.475) and decreased with respiratory virus co-infection (aOR 0.273, 95% CI 0.084-0.887). Elevated liver enzymes was significantly associated with the elevation of lactate dehydrogenase (aOR 3.055, 95% CI 2.257-4.137) and presence of pleural effusion (aOR 2.635, 95% CI 1.767-3.930) and proteinuria with respiratory virus co-infection (aOR 2.245, 95% CI 1.113-4.527). Conclusions: About 24% of pediatric MP patients were identified with various EPM. Since risk factors associated with each EPM was different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

РЕЗУЛЬТАТИ ВИВЧЕННЯ МІКРОБНОГО СПЕКТРУ У ДІТЕЙ З РОЗЛАДАМИ СПЕКТРУ АУТИЗМУ, АСОЦІЙОВАНИМИ З ГЕНЕТИЧНИМ ДЕФІЦИТОМ ФОЛАТНОГО ЦИКЛУ

Обґрунтування. Результати п’яти мета-аналізів рандомізованих контрольованих клінічних досліджень свідчать про асоціацію генетичного дефіциту фолатного циклу (ГДФЦ) і розладів спектру аутизму (РАС) у дітей. В таких випадках формується імунодефіцит та імунна дисрегуляція, що знижує резистентність до деяких мікроорганізмів.Мета дослідження: вивчити структуру мікробного спектру у дітей з РАС, пов’язаними з ГДФЦ, згідно з накопиченою дотепер доказовою базою і вивчити асоціацію виявлених мікроорганізмів з показниками імунного статусу для покращення розуміння патогенезу енцефалопатії та удосконалення алгоритмів діагностики, моніторингу і лікування.Матеріали і методи. Ретроспективно проаналізовано медичні дані 225 дітей віком від 2 до 9 років з ГДФЦ, у яких відзначалися клінічні прояви за типом РАС (досліджувана група; ДГ; 183 хлопчиків і 42 дівчинки). До контрольної групи (КГ) віднесли 51 клінічно здорову дитину (37 хлопчиків та 14 дівчаток) аналогічного вікового розподілу, які не страждали на ГДФЦ. Спеціальне лабораторне обстеження дітей груп спостереження проводили з урахуванням сучасних уявлень щодо мікробного спектру у пацієнтів з РАС згідно з публікаціями в PubMed і Embase. Для вивчення асоціацій між досліджуваними показниками застосовували показник відношення шансів (odds ratio, OR) та 95% довірчий інтервал (95% СІ). Дослідження виконувалося як фрагмент науково-дослідної роботи на замовлення МОЗ України (№ держреєстрації 0121U107940).Результати та їх обговорення. TTV відзначався в 87%, HHV-7 – 79%, HHV-6 – 68%, EBV – 59%, Streptococcus pyogenes – 46%, Candida albicans – 41%, Borrelia – 34%, Mycoplasma pneumoniae – 27%, Chlamydia pneumoniae – 26%, Yersinia enterocolitica – 23%, Toxoplasma gondii – 19%, перенесена природжена CMV нейроінфекція – 7%, наслідки HSV-1/2-нейро-інфекції – 5% випадків в ДГ (р<0,05; Z<Z0,05). HHV-6, HHV-7 та EBV були асоційовані з дефіцитами NK-, NKT- та СD8+ цитотоксичних Т-лімфоцитів. ТТV також був асоційований з дефіцитами NK- та NKT-лімфоцитів, однак не з дефіцитом СD8+ цитотоксичних Т-клітин. Стрептококова інфекція була пов’язана з гіпо- і дисімуноглобулінемією, а також – дефіцитом мієлопероксидази. Кандидоз був асоційований тільки з дефіцитом мієлопероксидази. Токсоплазмоз відзначався при дефіциті СD4+ Т-хелперів та комбінованих порушеннях імунітету. Наслідки природженої CMV-нейроінфекції мали місце тільки при комбінованих порушеннях імунітету. Висновки. Для дітей з РАС, асоційованими з ГДФЦ, характерним є специфічний мікробний спектр з переважанням інтрацелюлярних опортуністичних та умовно патогенних мікроорганізмів, який визначається особливостями порушень в імунному статусі, спровокованих ГДФЦ, що має визначати алгоритм раціонального мікробіологічногопошуку, оцінки імунного статусу, проведення антимікробного та імунотропного лікування.

Mycoplasma pneumoniae and Chlamydia pneumoniae Coinfection with Acute Respiratory Distress Syndrome: A Case Report

Community-acquired pneumonia caused by Mycoplasma pneumoniae or Chlamydia pneumoniae is usually mild. Mycoplasma pneumoniae-related and C. pneumoniae-related acute respiratory distress syndromes (ARDSs) are rare. Moreover, to our knowledge, there are no published reports on ARDS caused by M. pneumoniae and C. pneumoniae coinfection. Here, we report a case of an immunocompetent young woman who was co-infected with M. pneumoniae and C. pneumoniae and was started on treatment with piperacillin and clarithromycin. Two days later, she developed ARDS. She recovered rapidly following a change of antibiotic treatment to levofloxacin and was discharged on day 12. We conducted exome sequencing followed by alternative filtering to search for candidate ARDS-related genes. We identified an intronic variant of unknown significance within leucine-rich repeat-containing 16A (LRRC16A), a gene previously identified as a significant locus for platelet count with a possible role in ARDS. This is a rare case of ARDS in a young adult caused by M. pneumoniae and C. pneumoniae coinfection. This case suggests that ARDS in young adults may be correlated with variants in LRRC16A. This requires confirmation by further case reports.