Research

HIV research in focus

Early HIV treatment key to avoiding neurological damage

Early initiation of HIV treatment is key to avoiding brain atrophy and resulting long-term health consequences like memory loss, dementia and balance issues, new research has found.

While it has been known for some time that HIV-infection causes reduced volume and cortical thickness in some regions of the brain, it was unclear when these changes begin and what role combination antiretroviral therapy (cART) plays in stopping or slowing its progression.

To answer these questions, the study researchers from analysed  MRI data from 65 patients at the University of California, San Francisco, US, who had been infected less than one year before and compared it to that of 19 HIV-negative participants and 16 HIV-positive patients who had been infected for at least three years.

The researchers found that the longer the duration of untreated infection, the greater the volume loss and cortical thinning in several brain regions. Once cART treatment began, the volume changes in these regions stopped, and cortical thickness increased slightly in the frontal and temporal lobe.

These results, published in the journal Clinical Infectious Diseases, reinforce the need for early detection of HIV and delivery of cART as soon as possible to avoid neurological damage.

HIV infection can lead to memory loss, dementia later in life, and balance and vision problems, among other symptoms. Early screening and antiretroviral therapy can stop these symptoms before they occur, or stop their progression in patients who haven’t received fast enough treatment. At the end of 2016, there were 36.7 million people living with HIV, and of those, only 53 per cent had access to treatment.

“There have been few longitudinal structural neuroimaging studies in early HIV infection, and none that have used such sensitive analysis methods in a relatively large sample,” noted Mr Ryan Sanford, the study’s first author. “The findings make the neurological case for early treatment initiation and send a hopeful message to people living with HIV that starting and adhering to cART may protect the brain from further injury.”

Study links gut-homing protein levels with HIV infection risk, disease progression

For the first time, scientists have shown a relationship between the proportion of key immune cells that display high levels of a gut-homing protein called alpha-4 beta-7 at the time of HIV infection and health outcomes. Previous research illustrated this relationship in monkeys infected with a simian form of HIV.

The new study found that women who had more CD4+ T cells displaying high levels of alpha-4 beta-7 on their surface were more likely to become infected with HIV, and the virus damaged their immune systems more rapidly than women with fewer such cells.

“Our findings suggest that having a high frequency of alpha-4 beta-7-expressing CD4+ T cells, which HIV preferentially infects, leads to more HIV-infected CD4+ T cells moving to the gut, which in turn leads to extensive damage to gut-based immune cells,” said Dr Anthony S Fauci, co-author of the paper and Chief of the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases (NIAID).

The US National Institutes of Health co-funded the study with the South African Medical Research Council as part of the US-South Africa Programme for Collaborative Biomedical Research. In addition, NIH scientists collaborated on the study.

The research team compared the percentage of CD4+ T cells displaying high levels of alpha-4 beta-7 in blood samples drawn from 59 women shortly before they acquired HIV to the percentage of such cells in 106 women who remained HIV negative.

Aged 18-to-40 years, the women were selected from participants in the CAPRISA 004 study, which evaluated the safety and efficacy of tenofovir gel for HIV prevention in KwaZulu-Natal, South Africa, from 2007 to 2010.

Understanding HIV acquisition and disease progression among African women is especially important because women accounted for nearly 60 per cent of new HIV infections among adults in sub-Saharan Africa in 2016.

The proportion of CD4+ T cells with high levels of alpha-4 beta-7 had an effect, albeit modest, on the risk of acquiring HIV among both the women in the CAPRISA 004 study and a separate cohort of 41 female sex workers in Kenya. The risk of HIV acquisition rose by 18 per cent for each one per cent increase in alpha-4 beta-7 protein. The authors show a similar association in monkeys that were vaginally exposed to a simian form of HIV.

“These findings suggest that interventions in addition to ART may be needed to restore CD4+ T cells in the GI tracts of people living with HIV,” said Dr McKinnon. “One such intervention could be an anti-alpha-4 beta-7 antibody called vedolizumab, which is FDA-approved for the treatment of ulcerative colitis and Crohn’s disease.”

The report is published in the journal Science Translational Medicine.

Rising levels of HIV drug resistance

HIV drug resistance is approaching and exceeding 10 per cent in people living with HIV who are about to initiate or reinitiate first-line antiretroviral therapy, according to the largest meta-analysis to date on HIV drug resistance, led by researchers from UCL, the World Health Organisation (WHO) and part funded by the Bill and Melinda Gates Foundation.

The study, published in The Lancet Infectious Diseases, looked at data for people who were beginning antiretroviral therapy and found that resistance — particularly to one of the main types of first-line drug, non-nucleoside reverse transcriptase inhibitors (NNRTIs) — is increasing and those who exhibited drug resistance were more likely to have previously been exposed to antiretroviral drugs, often during pregnancy.

“Treatments for HIV have improved immensely in recent years, and close to 21 million people worldwide are now being treated with antiretroviral therapy. Yet to end the AIDS epidemic as a public health threat, minimising drug resistance will be one part of the response. Our findings show the importance of improving how we monitor drug resistance, and suggest we should review which drugs are included in first-line therapies,” said the study’s lead author Prof Ravindra Gupta.

The researchers pulled together 358 datasets, including data from 56,044 adults across 63 low- to middle-income countries who were beginning first-line therapy for HIV from 1996 and 2016. The research was conducted by a team of 33 authors on five continents.

Current WHO treatment guidelines for first-line therapy recommend NNRTIs in combination with nucleoside reverse transcription inhibitors (NRTI). The research team focused on studies that included data on the presence of drug-resistant mutations in the virus most commonly resistant to NNRTI drugs.

The research team found that, from 2001-2016, the odds of drug resistance in low- to middle-income countries across Sub-Saharan Africa, Latin America and Asia were increasing. In particular, the yearly incremental increase in NNRTI resistance was greatest in Eastern Africa (29 per cent annual increase) and in Southern Africa (23 per cent annual increase, with an absolute increase of 1.8 percentage points from 2015 to 2016) and was the smallest in Asia (11 per cent annual increase).

The study did not focus on high-income countries, but other studies have found that levels of drug resistance to NNRTIs in high-income countries were either plateauing or declining.

The study authors found drug resistance to be highest in Southern Africa, where 11.1 per cent of people beginning first-line therapy had a virus with NNRTI drug-resistant mutations, compared to 10.1 per cent in Eastern Africa, 7.2 per cent in Western/Central Africa, and 9.4 per cent in Latin America. The study team also found that people starting therapy who self-report previous use of antiretroviral drugs are more likely to carry resistant virus, and are at greater risk of virological failure.

Their data suggests that in some areas, 10-to-30 per cent of people presenting for antiretroviral therapy have previously been exposed to antiretroviral drugs. “Many people develop drug resistance after being treated by antiretroviral drugs if they stop taking their medication — often due to personal reasons, difficulty accessing treatment providers, or drug supply issues that are common in low-income regions. When these individuals restart treatment at a later date, they are less likely to respond to therapy and may pass on the drug-resistant strains to other people,” explained Prof Gupta.

If no action is taken, drug resistance to NNRTIs exceeding 10 per cent in people starting therapy could result in 890,000 more AIDS deaths and 450,000 more infections in Sub-Saharan Africa alone before 2030, as most people whose antiretroviral therapy is unsuccessful have a drug-resistant virus, according to prior research.

“If we are to combat HIV drug resistance, we must ensure countries can do a good job in monitoring and responding to it when needed,” said co-author Dr Silvia Bertagnolio of the WHO. “New WHO guidelines and a global action plan aim to help make this happen.”

WHO’s guidelines on pre-treatment HIV drug resistance recommend that countries switch to more robust first-line treatment when levels of resistance reach 10 per cent.

The five-year Global Action Plan calls on all countries and partners to join efforts to prevent, monitor and respond to HIV drug resistance and to protect the ongoing progress towards the Sustainable Development Goal of ending the AIDS epidemic by 2030.

Irish mums with HIV worried more about impact on their children than themselves — study

The immediate concern of Irish-based mothers upon diagnosis of HIV was for their babies and children, rather than themselves, as many minimise the significant personal impact of the news, according to new research.

In total, 11 women, five from Ireland, five from Africa and one from Europe, were interviewed for the narrative-based research report, ‘Frozen in a Moment of Time: The Experiences of Mothers Being Diagnosed with HIV Infection’.

Author of the report, Dr Denise Proudfoot of Dublin City University’s School of Nursing and Human Sciences, commented: “Few of the participants talked about personal responses following the diagnosis because their immediate worries were that they had infected their children with HIV, demonstrating that their response to a HIV positive diagnosis is strongly associated with maternal responsibilities.”

The variety and depth of testimony provides previously unheard-of accounts of these HIV-positive women with children, as little is known about their lives, she noted. “Upon diagnosis, participants were very much ‘frozen in a moment of time’ which they could not overcome until the HIV status of their children was known,” commented Dr Proudfoot.

The findings highlight that healthcare professionals need to be aware of how mothers-to-be and mothers worry about the possibility of infecting their children, despite the low likelihood of it happening due to HIV prevention interventions during pregnancy.

The study noted that although older children, born before their mothers were diagnosed with HIV, were unlikely to have the infection, “the possibility did concern mothers following diagnosis and most prioritised viral testing of their children”. Most of the study participants’ children were HIV-negative.

For these mothers, personal needs were secondary to those of their children and this indicated that healthcare professionals needed to adopt a “mother-centred” approach when supporting mothers living with HIV, as there is potential that they can neglect their own health, concluded Dr Proudfoot.

Over 8,000 people have been diagnosed with HIV in Ireland since testing began in the early 1980s. According to data from the Health Protection Surveillance Centre (HPSC), 508 people in Ireland were newly diagnosed with HIV in 2016, the majority of whom were gay men. However, approximately a quarter of those were female, mostly aged under 45 years and who may be mothers or pregnant when diagnosed.

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Potential cures for type 1 diabetes?

Type 1 diabetes is caused by the destruction of the insulin-producing cells in the pancreas and is primarily treated with daily insulin injections.

While incremental improvements in diabetes treatment are continuing, with pancreas and islet cell transplants offering effective options for some complex patients, there have been a number of recent research breakthroughs that point to potential long-term cures or even prevention of the condition.

For example, a preventive vaccine for type 1 diabetes is to be studied in humans for the first time this year after it was tested successfully in mouse models.

The connection between viral infections and type 1 diabetes has been researched for over 25 years at the University of Tampere in Finland.

Type 1 diabetes is becoming more common and cases of it occur in Finland more than elsewhere in the world.

A research group at the University of Tampere led by Prof Heikki Hyöty, Professor of Virology, has long pioneered the development of a vaccine that could prevent type 1 diabetes.

Their research indicates that one virus group, enteroviruses, play a part in developing type 1 diabetes. They can infect the insulin-producing cells in the pancreas and damage them permanently.

It has now been shown that a prototype enterovirus vaccine can protect against virus-induced type 1 diabetes in a mouse model.

“These exciting results showing that the vaccine completely protects against virus-induced diabetes, indicate the potential that such a vaccine has for elucidating the role of enteroviruses in human type 1 diabetes,” says Prof Malin Flodström-Tullberg at the Karolinska Institutet whose group were responsible for the pre-clinical studies.

“Already now it is known that the vaccine is effective and safe on mice. The developing process has now taken a significant leap forward as the next phase is to study the vaccine in humans,” says Prof Hyöty.

In the first clinical phase, the vaccine will be studied in a small group of adults to ensure the safety of the vaccine. In the second phase, the vaccine will be studied in children and the aim is to investigate both the safety of the vaccine and its effectiveness against enteroviruses. In the third phase, the aim is to investigate whether the vaccine could be used to prevent the onset of type 1 diabetes.

However, it can take about eight years in order to certainly know whether the vaccine prevents type 1 diabetes.

“The aim is to develop a vaccine that could prevent a significant number of type 1 diabetes cases. Additionally, the vaccine would protect from infections caused by enteroviruses, such as the common cold, myocarditis, meningitis and ear infections. However, in light of current research, the vaccine could not be used to cure existing diabetes,” explains Prof Hyöty.

The research phase beginning now is the result of a long period of negotiations between several stakeholders interested in the matter.

The research project will be funded by the US-based company Provention Bio. Other partners include the Juvenile Diabetes Research Foundation (JDRF), which is the largest foundation funding research on type 1 diabetes in the world.

Stem cells

Meanwhile, ViaCyte, a privately-held US regenerative medicine company is developing novel cell replacement therapies as potential long-term diabetes treatments to reduce the risk of hypoglycaemia and diabetes-related complications. 

ViaCyte’s product candidates are based on the derivation of pancreatic progenitor cells from stem cells, which are then implanted in durable and retrievable cell delivery devices.  Once implanted and matured, these cells are designed to secrete insulin and other pancreatic hormones in response to blood glucose levels.

The company has two product candidates in clinical-stage development. The PEC-Direct product candidate delivers the pancreatic progenitor cells in a non-immunoprotective device and is being developed for type 1 diabetes patients who have hypoglycaemia unawareness, extreme glycaemic lability, and/or recurrent severe hypoglycaemic episodes.

“Patients with high-risk type 1 diabetes complications, such as hypoglycaemia unawareness, are at constant risk of life-threatening low blood glucose,” said Dr Jeremy Pettus, investigator in the clinical trial and Assistant Professor of Medicine at UC San Diego, US. “The PEC-Direct islet cell replacement therapy is designed to help patients with the most urgent medical need.”

The PEC-Direct product candidate is currently in a phase 1/2 open-label clinical trial at multiple sites in the US and Canada to evaluate safety and efficacy.

In January the company announced that the first patients have been implanted in cohort two with a potentially efficacious dose of the company’s PEC-Direct islet cell replacement therapy.   

Cohort two is expected to enrol up to 40 patients and the primary efficacy measurement will be the clinically relevant production of insulin, as measured by the insulin biomarker C-peptide, in a patient population that has little to no ability to produce endogenous insulin at the time of enrolment. Other important endpoints will be evaluated including injectable insulin usage and the incidence of hypoglycaemic events.

“The implantation of a potentially efficacious dose of PEC-Direct marks an important milestone in the development of a functional cure for diabetes,” said Dr Paul Laikind, PhD, President and CEO of ViaCyte.

The company is also developing the PEC-Encap (also known as VC-01) product candidate, which delivers the same pancreatic progenitor cells in an immunoprotective device and is being developed for all patients with diabetes, type 1 and type 2, who use insulin. 

About 10 per cent of type 1 diabetes patients have high-risk type 1 diabetes. 

These patients are often eligible for islet transplants in countries that provide them (currently not available in Ireland).

“Islet transplants have been used to successfully treat patients with unstable, high-risk type 1 diabetes, but the procedure has limitations, including a very limited supply of donor organs and challenges in obtaining reliable and consistent islet preparations,” noted trial investigator Dr James Shapiro, Director of the Clinical Islet Transplant Programme, University of Alberta, US. “An effective stem cell-derived islet replacement therapy would solve these issues and has the potential to help a greater number of people.”

The PEC-Direct product candidate could overcome some of the key limitations of islet transplant by providing a virtually unlimited supply of cells manufactured under quality-controlled conditions, with a potentially safer and more optimal route of administration.

The PEC-Direct product candidate delivers stem cell-derived PEC-01 pancreatic progenitor cells in a device designed to allow direct vascularisation of the cells, which is expected to allow for a robust engraftment and cellular performance similar to the anatomy of a normal islet. Given the open nature of the device, patients implanted with PEC-Direct, as with other transplants, will require immune suppression.

Thus, PEC-Direct is being developed to treat patients with the greatest unmet medical need, including type 1 diabetes patients who already require immune suppression following a kidney transplant, as well as type 1 patients who are at high-risk for acute complications, such as hypoglycaemia unawareness, extreme glycaemic lability, and/or severe hypoglycaemic episodes.

ViaCyte recently announced funding from the California Institute for Regenerative Medicine (CIRM) to support yet another potentially transformative cell therapy approach that could be used for the treatment of diabetes. The company plans to engineer its CyT49 pluripotent stem cell line to be immune evasive, which it says, if successful, would open up off-the-shelf therapeutic applications in a number of fields.

ViaCyte is headquartered in San Diego, California, US, and is also funded in part by the JDRF.

 


Diabetes Ireland seeks parity of access to new blood glucose-monitoring technology for type 1 diabetes patients

Diabetes Ireland is calling on the HSE to reimburse a flash glucose monitoring system that does not require finger blood pricks for all type 1 diabetics.

In January Minister for Health Simon Harris announced that the continuous monitoring technology was being reimbursed only for children and young adults who require multiple dose injections of insulin in the first instance.

Diabetes Ireland said it is extremely disappointed that the Freestyle Libre technology is not being made available for every person with type 1 diabetes based on their clinical need.  “We are very much aware of the many disappointed adults, who currently pay up to €120 a month for this device and have seen much improvement in their health and quality-of-life from using the device daily over the past 12 months.

“A lot of these adults were encouraged to get the device by their diabetes team, based on their clinical need, and on the basis that it would eventually be reimbursed by the HSE, as it is in the UK and many other countries.”

Almost 19,000 people have now signed an online petition created by diabetes advocate, Davina Lyon, campaigning for reimbursement of the device for all people with type 1 diabetes.

There are approximately 20,000 people with type 1 diabetes in Ireland, Diabetes Ireland said. According to the 2012 Irish Paediatric Diabetes Audit, there are 2,750 children under 16 years with type 1 diabetes. With the current restrictions on the reimbursement scheme only a small percentage of those children will be included and 17,000 adults with type 1 diabetes completely excluded because of their age, Diabetes Ireland pointed out.

It said that the HSE used the Health Technology Assessment Group (HTAG) advice note to estimate that the “average additional cost per patient per year for using Freestyle Libre is a minimum of €62.60” making the cost of providing the Libre to all people with type 1 diabetes approximately €1.2 million, with an estimated additional saving in the “expected reduction in the need to perform finger prick testing of over 2,000 times per year”.

Diabetes Ireland said this is “an insult to the diabetes community as the HSE has already saved €5 million on blood glucose strips since April 1, 2016, when the rules governing access to blood glucose strips for people with type 2 diabetes were changed”.

Representatives from the diabetes community have requested a meeting with Minister Harris to discuss their concerns and to present the online petition.

Diabetes Ireland reiterated that it is very supportive of the Type 1 Diabetes Community Advocacy Group position and firmly believes that everyone with type 1 diabetes should have access to the technology that bests support them to clinically manage their condition most effectively on a daily basis.

“However, it seems in this instance the HSE decision was based more on a cost basis rather than from the perspective of the patient’s quality-of-life and clinical need.”

Further information from the HSE in a response to a recent Parliamentary Question by Ms Mary Butler, TD, about the patient eligibility criteria for Freestyle Libre, is causing more confusion as it is not made clear whether a person needs to meet just one of the criteria, or all of the criteria to qualify for the technology.

“If it is the case that all of the criteria need to be met, then only a very small group of people will be eligible and this is not acceptable. The HSE will be asked to further clarify and explain its position on this issue,” said Diabetes Ireland.

 

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Cardiology initiatives from the West

The heart and stroke charity Croí, which is based in Gal­way, has recently expanded its multidisciplinary health team at the Heart and Stroke Cen­tre in the city. The charity, which was founded in 1985 and continues to support the development of cardiac and stroke services in the region, is leading the way in designing and test­ing lifestyle and behaviour change models of care focused on disease prevention and rehabilitation.

As an example of this, Croí is en­gaged in developing a model of community cardiac rehabilita­tion, which could supplement ex­isting programmes that are hospi­tal-based. This is a HSE Health and Wellbeing Division-funded initia­tive to address the identified need for increased and standardised provision of cardiac rehabilitation, which is a priority of the Health and Wellbeing Division, for imple­mentation under the HSE’s Nation­al Framework for Self-Management Support for Chronic Conditions. This project aims to examine the feasibility of providing community-based cardiac rehabilitation and de­termining the effectiveness and scal­ability of such a programme in an Irish setting. The initiative, which is based on the Croí MyAction Pro­gramme, meets the British Asso­ciation of Cardiac and Pulmonary Rehabilitation (BACPR) standards and core competencies.

””

Mr Neil Johnson, CEO, Croi

A needs assessment of cardiac re­habilitation (phase 3) in Ireland, car­ried out in 2016, found that only 39 per cent of the need for cardiac re­habilitation is met by current capac­ity nationally, at the narrowest defi­nition of need (ie, patients admitted to hospital with acute coronary syn­drome; post-revascularisation; or heart failure). The gap in provision is variable around the country and similar in the Saolta Hospital Group to the national picture. When you broaden the criteria for referral to in­clude patients with a wider range of conditions for which cardiac rehab is recommended, the deficit is even greater. Expansion of current capac­ity by a minimum of 61 per cent is re­quired nationally.

Ideally, the development of a community-based cardiac rehabil­itation programme should contrib­ute to increased access and availa­bility of cardiac rehab for the pop­ulation and support current hospi­tal provision, which is delivered by excellent cardiac rehab co-ordina­tors and staff who have been oper­ating against a backdrop of signifi­cant cutbacks in recent years.

Leadership in prevention and recovery

In 2014, Croí launched the Na­tional Institute for Preventive Car­diology (NIPC), affiliated to the College of Medicine, Nursing and Health Sciences at NUI Galway. The aims of the Institute are to pro­vide leadership through discovery, training and applied programmes in the prevention and control of cardiovascular disease; promote healthier living; raise the standards of preventive cardiology practice; and prepare leaders to advance pre­ventive healthcare in Ireland. Cur­rently, over 1,200 healthcare pro­fessionals, educators and research­ers have joined the NIPC Alliance, which provides regular updates on latest research, highlights hot top­ics, and profiles upcoming training and education opportunities. Mem­bership of the NIPC Alliance is free — see www.nipc.ie for further de­tails and to sign-up for the month­ly e-bulletin.

NIPC education and training op­portunities include an MSc Degree and Postgraduate Diploma in Pre­ventive Cardiology at NUI Galway, associated with the founding pro­gramme at Imperial College Lon­don. Applications are now open for the fifth year of this programme, which commences in September 2018. This level 9 course, which uses blended learning, is available as a one-year, full-time, in-service programme leading to an MSc, or a nine-month, full-time, in-service programme leading to a PG Diplo­ma. Further details are available at www.nuigalway.ie/medicine.

Other upcoming NIPC education and training opportunities include a ‘Cholesterol Masterclass’, which takes place in the Herbert Park Ho­tel, Dublin, on Friday, 27 April. Key sessions include: Updates on ‘Li­pid Guidelines for Optimal Man­agement’ by Dr Patricia O’Connor, Consultant Physician and Clinical Pharmacologist, St James’s Hospi­tal, Dublin; ‘Management of Lipids in Special Populations’ by Dr Der­mot Neely, Consultant in Clinical Bi­ochemistry and Metabolic Medicine, Newcastle upon Tyne NHS Trust; ‘Statin Intolerance — the Contro­versies’ by Dr Susan Connolly, Con­sultant Cardiologist, Western Health and Social Care Trust, Northern Ire­land; ‘Familial Hypercholesterolae­mia in Ireland’ by Dr Vivion Crow­ley, Consultant Chemical Pathol­ogist, St James’s Hospital, Dub­lin; and ‘Challenges to Adherence’ with Dr Joe Gallagher, GP, Wex­ford. Register for free at www.nipc. ie/conferences.html.

Another upcoming NIPC course which may be of interest to GPs, hospital doctors, nurses and other healthcare professionals is a one-day workshop, ‘Demystifying the ECG’, which takes place in the Croí Heart and Stroke Centre, Galway, on Saturday, 24 March. This excel­lent training course is delivered by Dr Paul Nolan, BSc ASCST, Chief Cardiac Physiologist at Galway University Hospital. Registration is now open at www.nipc.ie.

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Asthma and fertility in women

Women with asthma who only use short-acting asthma relievers take longer to become pregnant than other women, according to a new study published in the European Respiratory Journal.

However, the study of more than 5,600 women in Ireland, Australia, New Zealand and the UK also shows that women with asthma who use long-acting asthma preventers conceive as quickly as other women.

While maternal asthma has been consistently associated with significant perinatal morbidities and mortality, impacts on fertility are conflicting, according to the study authors. In light of limited and conflicting evidence, the aim of the study (‘Asthma treatment impacts time to pregnancy: Evidence from the international SCOPE study’) was to examine the impact of asthma and asthma medication use on fecundability and time to pregnancy.

The researchers examined data from the international Screening for Pregnancy Endpoints (SCOPE) study, which recruited more than 5,600 women expecting their first babies in the early stages of pregnancy.

Ten per cent of women in the study said they had asthma and, overall, these women took longer to get pregnant.

When researchers separated this group according to the types of asthma treatments they were using, they found no difference in fertility between women using long-acting asthma treatments and women without asthma.

Women using short-acting reliever medication (beta-agonists) took 20 per cent longer to conceive on average. They were also 30 per cent more likely to have taken more than a year to conceive, which the researchers defined as the threshold for infertility.

This difference remained even after researchers took other factors known to influence fertility, such as age and weight, into account.

The study was led by Dr Luke Grzeskowiak from the University of Adelaide’s Robinson Research Institute, who said that the results provide reassurance for asthmatic women that using inhaled corticosteroids to prevent symptoms does not appear to reduce fertility.

“Five-to-10 per cent of all women around the world have asthma and it is one of the most common chronic medical conditions in women of reproductive age. Several studies have identified a link between asthma and female infertility, but the impact of asthma treatments on fertility has been unclear,” Dr Grzeskowiak said.

“Studying the effect of asthma treatments in women who are pregnant or trying to get pregnant is important, as women often express concerns about exposing their unborn babies to [the] potentially harmful effects of medications.”

While the study showed that women using short-acting asthma relievers take longer to get pregnant, “on the other hand, continued use of long-acting asthma preventers to control asthma seems to protect fertility and reduce the time it takes women with asthma to become pregnant. This could lead to a reduction in the need for fertility treatments”.

“There is plenty of evidence that maternal asthma has a negative impact on the health of pregnant mothers and their babies, and so our general advice is that women should take steps to get their asthma under control before trying to conceive,” he said.

“What we don’t yet know is exactly how asthma or asthma treatments lead to fertility problems. As well as affecting the lungs, asthma could cause inflammation elsewhere in the body, including the uterus. It could also affect the health of eggs in the ovaries.

“Inhaled corticosteroids suppress the immune system, whereas short-acting asthma treatments do not alter immune function. In women who are only using relievers, it’s possible that, while their asthma symptoms may improve, inflammation may still be present in the lungs and other organs in the body.”

The researchers plan further studies involving women with asthma who are undergoing fertility treatments, to see whether improving asthma control could also improve fertility outcomes.

Meanwhile, a separate study presented at the 2017 European Respiratory Society International Congress in Milan found that women with asthma are more likely to have fertility treatment before giving birth than non-asthmatic women.

Among 744 pregnant asthmatic women enrolled in the ‘Management of Asthma During Pregnancy’ programme at the Hvidovre Hospital, Hvidovre, Denmark, and who gave birth between 2007 and 2013, 12 per cent had received fertility treatment compared to 7 per cent of the 2,136 non-asthmatic women in the control group.

Although the study does not prove that asthma played a role in reducing fertility in some women, the researchers said it suggests that improving women’s asthma control might help them to become pregnant more easily.

Prof Charlotte Suppli Ulrik, from the Department of Respiratory Medicine at Hvidovre Hospital, who supervised the study, said: “We don’t have the hard-core evidence but based on what we know, it seems very likely that good asthma control will improve fertility in women with asthma by reducing the time it takes to become pregnant and, therefore, the need for fertility treatment.

“However, when it comes to fertility for women, age is a crucial factor — so the message, particularly for women with asthma, is don’t wait too long, as it might reduce your chances of having children.”

Prof Suppli Ulrik and colleagues are setting up studies to investigate further the association between asthma and fertility, including a study addressing the impact of good asthma control on fertility. “Further studies are needed to confirm our findings,” she said.

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