Airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis.

J Inflamm Res. 2013;6:1-11

Authors: Bergin DA, Hurley K, Mehta A, Cox S, Ryan D, O'Neill SJ, Reeves EP, McElvaney NG

Abstract
Bronchiectasis is an airway disease characterized by thickening of the bronchial wall, chronic inflammation , and destruction of affected bronchi. Underlying etiologies include severe pulmonary infection and cystic fibrosis (CF); however, in a substantial number of patients with non-CF-related bronchiectasis (NCFB), no cause is found. The increasing armamentarium of therapies now available to combat disease in CF is in stark contrast to the limited tools employed in NCFB. Our study aimed to evaluate similarities and differences in airway inflammatory markers in patients with NCFB and CF, and to suggest potential common treatment options. The results of this study show that NCFB bronchoalveolar lavage fluid samples possessed significantly increased NE activity and elevated levels of matrix metalloproteinases 2 (MMP-2) and MMP-9 compared to healthy controls (P < 0.01); however, the levels detected were lower than in CF (P < 0.01). Interleukin-8 (IL-8) concentrations were significantly elevated in NCFB and CF compared to controls (P < 0.05), but in contrast, negligible levels of IL-18 were detected in both NCFB and CF. Analogous concentrations of IL-10 and IL-4 measured in NCFB and CF were statistically elevated above the healthy control values (P < 0.05 and P < 0.01, respectively). These results indicate high levels of important proinflammatory markers in both NCFB and CF and support the use of appropriate anti-inflammatory therapies already employed in the treatment of CF bronchiectasis in NCFB.

PMID: 23426081 [PubMed]

Isolation and characterization of current human coronavirus strains in primary human epithelia cultures reveals differences in target cell tropism.

J Virol. 2013 Feb 20;

Authors: Dijkman R, Jebbink MF, Koekkoek SM, Deijs M, Jónsdóttir HR, Molenkamp R, Ieven M, Goossens H, Thiel V, van der Hoek L

Abstract
The human airway epithelium (HAE) represents the entry port of many human respiratory viruses, such as human coronaviruses (HCoVs). Nowadays, four HCoVs, HCoV-229E, HCoV-OC43, HCoV-HKU1 and HCoV-NL63, are known to circulating worldwide, which cause upper and lower respiratory tract infections in non- and hospitalized children. Still studies on fundamental aspects of these HCoV infections at the primary entry port, such as cell tropism are seriously hampered by the lack of a universal culture system, or suitable animal models. To expand the knowledge on fundamental virus-host interactions of all four HCoVs at the site of primary infection, we used pseudo-stratified HAE cell cultures to isolate and characterize clinical representative HCoV strains directly from nasopharyngeal material. Ten contemporary isolates were obtained representing HCoV-229E (n = 1), HCoV-NL63 (n = 1), HCoV-HKU1 (n = 4) and HCoV-OC43 (n = 4). From each strain we analyzed the replication kinetics and progeny virus release on HAE cell cultures derived from different donors. Surprisingly, by visualizing HCoV infection using confocal microscopy, we observed that HCoV-229E employs a target cell tropism for non-ciliated cells whereas HCoV-OC43, HCoV-HKU1 and HCoV-NL63 all infect ciliated cells. Collectively, we demonstrate that HAE cell cultures, that morphologically and functionally resemble human airways in vivo, represent a robust universal culture system to isolate and compare all contemporary HCoV strains.

PMID: 23427150 [PubMed - as supplied by publisher]

[Post-infectious bronchiolitis obliterans].

Rev Mal Respir. 2013 Feb;30(2):152-60

Authors: de Blic J, Deschildre A, Chinet T

Abstract
Post-infectious bronchiolitis obliterans (BO) is characterized by inflammatory and fibrotic lesions of small airways following a pulmonary infection and leading to some degree of airway obstruction. It represents a rare cause of chronic obstructive pulmonary disease, and is probably underestimated, especially when the lesions affect small areas of the lungs. The clinical features differ between children and adults. In children, adenovirus is the most frequently involved infectious agent, especially the more virulent serotypes 3, 7 and 21. The clinical and radiological signs vary widely and the functional outcome depends on the extent of the lung injury. The diagnosis is based on the medical history, the CT-scan and functional data. The treatment is symptomatic. The most severe forms may result in chronic respiratory insufficiency. In adults, the frequency of obstructive injuries of the small airways in the context of lung infection is unclear. Parenchymal lesions are often present, resulting in BO with organizing pneumonia. These lesions alter the clinical presentation and the radiographic features of the initial infectious disease and often prove difficult to diagnose and manage. Several authors have published clinical cases describing presumed efficacy of systemic corticosteroids but the data are scarce.

PMID: 23419446 [PubMed - in process]

Meta-analysis: Procalcitonin-guided antibiotic therapy reduces treatment failure in acute respiratory infection.

Ann Intern Med. 2013 Feb 19;158(4):JC2-5

Authors: Jagminas L

Abstract
QUESTION What are the relative efficacy and safety of procalcitonin (PCT)-guided initiation and discontinuation of antibiotic therapy compared with usual care in adults with acute respiratory infection (ARI)? REVIEW SCOPE Included studies compared PCT-based antibiotic therapy initiation or discontinuation strategies with a control group without knowledge of PCT level or use of alternative biomarkers in adults with ARIs. Outcomes were treatment failure and mortality. Secondary outcomes included antibiotic use. REVIEW METHODS Cochrane Central Register of Controlled Trials (Issue 2, 2011), which includes MEDLINE and EMBASE/Excerpta Medica (May 2011) and Acute Respiratory Infections Group Specialised Register (Jun 2011), was searched for randomized controlled trials (RCTs). Trials that exclusively focused on pediatric patients or used procalcitonin to escalate antibiotic therapy were excluded. 14 RCTs (n = 4211) met the inclusion criteria: 10 had adequate generation of the randomization sequence, 7 had adequate allocation concealment, and 5 had blinded outcome assessors. Follow-up varied from hospital discharge or 14 to 21 days to 1 month. Community-acquired pneumonia was the most common ARI diagnosis. MAIN RESULTS Adherence to algorithms varied from 47% to 91%. Individual patient data meta-analyses showed that PCT-guided antibiotic therapy reduced treatment failure but not mortality compared with usual care (Table). The PCT-guided group had less antibiotic exposure than the usual care group (median 4 vs 8 d, P &lt; 0.001). CONCLUSION Procalcitonin-guided initiation and discontinuation of antibiotic therapy reduced treatment failure but not mortality compared with usual care in adults with acute respiratory infection.Individual patient meta-analysis of procalcitonin (PCT)-guided antibiotic therapy vs usual care for acute respiratory tract infections in adults*OutcomesNumber of trials (n)Weighted event ratesAt ≤ 1 monthPCT-guidedUsual careRRR (95% CI)NNT (CI)Treatment failure14 (4211)19%22%15% (2 to 24)32 (19 to 194)Mortality14 (4211)5.9%6.3%6% (-21 to 28)Not significant*Abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rates and adjusted odds ratios in article.

PMID: 23420253 [PubMed - in process]