Longitudinal Changes in Spirometry in South African Adolescents Perinatally Infected With Human Immunodeficiency Virus Who Are Receiving Antiretroviral Therapy.


  • 影响因子:5.31
  • DOI:10.1093/cid/ciz255
  • 作者列表:"Githinji LN","Gray DM","Hlengwa S","Machemedze T","Zar HJ
  • 发表时间:2020-01-16

BACKGROUND:Despite increased access to highly active antiretroviral therapy (HAART), lung disease remains common in human immunodeficiency virus (HIV)-infected (HIV+) adolescents. There is limited information on changes in lung function over time in perinatally HIV+ adolescents on HAART. The objective was to investigate the progression of spirometry findings over 2 years in HIV+ adolescents on HAART in a prospective cohort, the Cape Town Adolescent Antiretroviral Cohort (CTAAC). METHODS:HIV+ adolescents aged 9-14 years, with at least 6 months of HAART, and a comparator group of healthy HIV-uninfected (HIV-), age-matched controls were enrolled in CTAAC. Spirometry and bronchodilator testing were done at baseline, 12 months, and 24 months. Mixed-effect models were used to compute longitudinal changes in lung function. RESULTS:Five hundred fifteen HIV+ adolescents, mean age 12 (standard deviation [SD], 1.6) years, 50.4% male, and 110 HIV- adolescents, mean age 11.8 (SD, 1.8) years, 45.6% male, were tested at baseline; 477 (93%) HIV+ and 102 (93%) HIV- adolescents at 12 months; and 473 (92%) HIV+ and 97 (88%) HIV- adolescents at 24 months. Only 5.4% of the HIV+ adolescents had HIV viral load >10 000 copies/mL at baseline. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were lower in the HIV+ compared to the HIV- adolescents and tracked with no deterioration or catch-up over 2 years. Previous pulmonary tuberculosis (PTB) or lower respiratory tract infection (LRTI) was significantly associated with reduced FEV1 and FVC (P < .05 for both). CONCLUSIONS:HIV+ adolescents had lower lung function over 2 years than HIV- adolescents. This study highlights the need for lung function surveillance and prevention of LRTIs and PTB in HIV+ adolescents.


背景: 尽管获得高效抗逆转录病毒治疗 (HAART) 的机会增加,但肺部疾病在人类免疫缺陷病毒 (HIV) 感染 (HIV +) 的青少年中仍然很常见。关于 HAART 上围产期 HIV + 青少年肺功能随时间变化的信息有限。目的是在一项前瞻性队列,即开普敦青少年抗逆转录病毒队列 (CTAAC) 中,调查 HIV + 青少年接受 HAART 治疗 2 年以上肺活量测定结果的进展。 方法: 9-14 岁的 HIV + 青少年,至少 6 个月的 HAART,以及健康 HIV 未感染 (HIV-) 的对照组,年龄匹配的对照入组 CTAAC。在基线、 12 个月和 24 个月时进行肺活量测定和支气管扩张剂检测。混合效应模型用于计算肺功能的纵向变化。 结果: 1.6 名 HIV + 青少年,平均年龄 12 (标准差 [SD],50.4%) 岁,110 名男性,11.8 名 HIV-青少年,平均年龄 1.8 (SD,) 年,45.6% 为男性,基线检测; 477 (93%) HIV + 和 102 (93%)12 个月时的 HIV-青少年; 24 个月时 473 (92%) HIV + 和 97 (88%) HIV-青少年。仅 5.4% 的 HIV + 青少年基线时 HIV 病毒载量> 10 000 拷贝/mL。1 秒用力呼气容积 (FEV1) 和用力肺活量 (FVC) 与 HIV-青少年相比,HIV + 的患病率较低,并且在 2 年内没有恶化或追赶。既往肺结核 (PTB) 或下呼吸道感染 (LRTI) 与 FEV1 和 FVC 降低显著相关 (P <.05)。 结论: HIV + 青少年在 2 年内肺功能低于 HIV 青少年。本研究强调了在 HIV + 青少年中进行肺功能监测和预防 LRTIs 和 PTB 的必要性。



作者列表:["De Cunto G","Brancaleone V","Riemma MA","Cerqua I","Vellecco V","Spaziano G","Cavarra E","Bartalesi B","D'Agostino B","Lungarella G","Cirino G","Lucattelli M","Roviezzo F"]

METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.

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作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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作者列表:["Zaragosi LE","Deprez M","Barbry P"]

METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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