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limitation of this study “is the inability to tease out the effects of HIV co-infection”.

Taraz Samandari (Centers for Disease Control and Prevention, Atlanta, GA, USA) says, the results “underscore the critical importance of setting up isoniazid preventive therapy programs that ensure high uptake and high adherence in order to impact tuberculosis incidence”. He adds, “with the growing docu mentation in global surveys of isoniazid resistance and multidrug-resistant tuberculosis, it will be important to identify the background isoniazid resistance threshold at which isoniazid preventive therapy loses its effectiveness in preventing tuberculosis disease.”

Giovanni Battista Migliori (WHO Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S Maugeri, Care and Research Institute, Tradate, Italy) praises Churchyard and colleagues for their “boldness in

replicating Comstock and colleagues’ study of the 1960s” and testing of “the often dismissed hypothesis of the potential impact of large-scale preventive treatment in controlling tuberculosis”. However, in his opinion, the investigators’ conclusions are “far too pessimistic and do not do justice to the value of preventive treatment”, which “is highly effi cacious and off ers a high level of individual protection”. In the study, tuberculosis incidence was reduced by 58% during the 9 months in individuals who started isoniazid preventive therapy. Hence, Migliori advises, “we must not fall into the now centenary paradigm, if not mistake, of looking at the value of tuberculosis interventions exclusively from a community perspective. If a preventive treatment off ers this level of individual protection, its clinical and individual direct value should be duly recognised.”

Farhat Yaqub

Eff ectiveness of tuberculosis preventive therapy in gold minersGavin Churchyard and colleagues report that community-wide isoniazid preventive therapy for 9 months did not reduce the incidence (adjusted rate ratio 0·96, 95% CI 0·76–1·21; p=0·71) and prevalence (adjusted prevalence ratio 0·98, 0·65–1·48; p=0·90) of tuberculosis in South African gold miners in the intervention clusters compared with control clusters in their randomised study. Keertan Dheda (Division of Pulmonology, University of Cape Town, and Groote Schuur Hospital, Cape Town, South Africa) thinks these fi ndings “likely refl ect very high early transmission rates and the susceptibility of the population studied”. Miners often live in crowded hostels or informal housing and have several susceptibility risk factors, including HIV, nutritional deficiencies, tobacco smoking, and exposure to silica dust, and this, he remarks, “creates a perfect storm for acquisition of tuberculosis”. Like the investigators, Dheda notes that a

Published OnlineFebruary 3, 2014http://dx.doi.org/10.1016/S2213-2600(14)70004-9

For Gavin Churchyard and colleagues’ report see N Engl J Med 2014; 370: 301–10

For the Comstock and colleagues’ study see Am Rev Respir Dis 1967; 95: 935–43

For more about preventive treatment see Eur Respir J 2013; 42: 785–801

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First stem cell treatment for BPD in preterm infantsA research team has successfully transplanted human umbilical cord blood-derived stem cells (hUCB) into preterm infants to treat broncho-pulmonary dysplasia (BPD).

The phase 1 dose-escalation study, published in the American Journal of Pediatrics, looked at the safety and feasibility of administration of a single intratracheal dose of hUCB-derived mesenchymal stem cells (MSCs) into nine very-pre-term infants (24–26 weeks gestational age) who were at high risk of developing BPD (on ventilator support with deteriorating respiratory condition).

Results of the study by Won Soon Park and colleagues (Samsung Medical Center and Biomedical Research Institute, Seoul, South Korea), showed that three of nine (33%) treated infants developed moderate BPD, with none developing severe BPD, compared with

13 of 18 (72%) in the matched control group who developed moderate or severe BPD.

Three of the infants received a low dose (1 × 107 cells/kg) and six received a high dose (2 × 107 cells/kg) of stem cells. All of the treated infants tolerated the procedure, although six subsequently developed serious adverse events. Patent ductus arteriosus ligation occurred in four of nine patients (44%), with one of these patients developing pneumothorax. However, no sig-nifi cant diff erence in serious adverse events was noted between the treated and control group or the high-dose and low-dose groups.

Professor Stella Kourembanas (Harvard Medical School, Boston, MA, USA), commenting on the research, said: “The findings of this study are important in establishing both feasibility and short-term safety of MSC

administration in pre-term infants who are at high risk for developing BPD. This successful phase I trial opens the door to more extensive clinical trials where the right dosing, timing, efficacy, and long-term safety of MSC-based therapies can be tested.”

She added: “Before it can become standard treatment, it is imperative that long-term safety be established to ensure that the low but theoretical risk of tumour formation is investigated in well designed follow-up studies.”

Dr Park told The Lancet Respiratory Medicine, “We are currently looking at the low dose of cells in our phase II clinical trial (NCT01828957) and, if successful, our next step may be using an even lower dose of cells. The phase II trial should be completed in 2015 and reported by 2016”.

Hilary Marshall

Published OnlineFebruary 24, 2014http://dx.doi.org/10.1016/S2213-2600(14)70007-4

For the paper by Yun Sil Chang et al see J Pediatrics 2014; DOI:10.1016/j.jpeds.2013.12.011

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