An international Task Force has recommended a method to help diagnose preschool age children with Primary Ciliary Dyskinesia (PCD), a rare, inherited condition that leads to chronic lung, ear and sinus infections. The Task Force’s findings were published in the European Respiratory Journal.
Children with PCD have a problem with mucus build-up, which leads to inflammation in the airways and infections in the lungs, nose, sinuses and ears. Most people with PCD have symptoms from birth or early childhood. But some children with PCD may not be diagnosed until much later.
Currently, a commonly used diagnostic test for PCD is measuring the nitric oxide (nNO) in the nose using a chemiluminescent analyser. This involves holding a sampling tube at the nostril, whilst the patient either holds their breath, or breathes out through their mouth against a resistance – but for young children such controlled breathing isn’t always practical. Furthermore, chemiluminescence analysers are extremely expensive, not portable, and not available in most countries.
Jane Lucas, Professor of Paediatric Respiratory Medicine at University of South Hampton, led an international Task Force to review existing studies and literature to establish whether there were more effective and accessible methods of diagnosis for PCD in younger children.
The task force concluded that although holding the breath or breathing against a resistor whilst using a chemiluminescence analyser was more reliable in older children and adults, adequate measurements could be achieved by measuring nasal nitric oxide whilst a pre-school child breathes normally and should be the standard way when diagnosing PCD in children under the age of five.
The Task Force also suggested that although chemiluminescence analysers are more reliable, the relatively inexpensive electrochemical devices have a role in healthcare systems with limited resources. They also recognised that the portability of electrochemical devices may be useful in countries where patients live long distances from a specialist centre, enabling the specialist to travel to the patient.
“We know that the earlier we can diagnose a condition, the better the chances are of implementing the best treatment plan for the patient,” Professor Lucas said. “But current guidelines and technical standards focus on nNO measurements in older, cooperative children using technology that is not widely available.
“Pre-schoolers often need different methods to be employed when measuring nNO, methods that are less invasive and adaptable. Without guidelines for younger children, and electrochemical analysers there is huge variability in how people take the measurements and interpret them.
“This paper is the first step towards standardising sampling, analysis, and reporting of nNO measured as part of the diagnostic testing for PCD in all age groups including preschool-age children. We hope this will promote earlier diagnosis of PCD, and a standardised approach to interpreting and reporting results.”
The task force also recommends that future research is needed to ensure the technical standard is kept up to date.
Despite being one of the most common non-communicable diseases globally and there being highly effective treatments for it, asthma is often not well controlled in many low-resource settings, according to a cross-sectional study recently published in the Lancet medical journal.
Closer to home, the Global Asthma Report from 2022 showed that there has been an increase in severe asthma symptoms among adolescents in Cape Town over the last few years. There is little data available for the rest of the country, which makes comparisons with other South African cities very tricky.
‘Disproportionate number of children have severe asthma’
Dr Ahmed Ismail Manjra, a paediatrician and allergologist at the Allergy and Asthma Centre in Durban, tells Spotlight that globally more children than adults have asthma. The centre is in the Life Westville Hospital and provides specialist services to adults and children with asthma or allergic disorders.
“Asthma is quite common in children. It is estimated [globally] that one in ten children have asthma, and in adults, the prevalence is less than in children,” he says. “But the problem is that in South Africa we see a disproportionate number of children with severe asthma. And what has been shown is that over the years the prevalence of asthma is rising, and the severity is rising.” (For more on what asthma is and how it is treated in South Africa’s public sector, see this Spotlight article from December 2022.)
Impact of undiagnosed uncontrolled asthma
The impact of undiagnosed or uncontrolled asthma on children is huge. First, according to Professor Refiloe Masekela, Paediatric Pulmonologist and the Head of Department of Paediatrics and Child Health at the University of KwaZulu-Natal, the symptoms are very noticeable, which can affect children socially. Secondly, a child with undiagnosed asthma will miss school because of their symptoms and be unable to participate in school activities like sport. They will also become less active because exercise may trigger symptoms, which have further effects on their health.
Another implication of uncontrolled asthma, according to Manjra, is poor sleep quality, which can impact a child’s academic performance.
“And in severe asthma without proper treatment, it can lead to recurrent admissions to hospital. This places a burden on the healthcare system, which can be easily prevented by proper management of asthma. And of course, in a small percentage of cases where the asthma is not well controlled, it can also lead to fatality,” he says.
Manjra urges parents to take their children to be checked for asthma if they have recurrent respiratory symptoms.
“The asthma treatment is extremely effective, very safe as well, [and] they have very few side effects. Parents should not be afraid to use asthma treatments to control their children’s asthma,” he says. “Although we don’t have a cure for asthma, we do have medicines that can control it and give better quality of life.”
Asthma trends in children: what the data says
Masekela explains that the data published in the Global Asthma Report is published by the Global Asthma Network (GAN), which consists of a network of centres across the world – including three in South Africa – that contribute data on asthma in their regions every few years.
This data collection effort started with the ISAAC one and ISAAC three studies (International Studies of Asthma and Allergens in Children). The GAN centre in Cape Town contributed data to ISAAC I in 1995 and for ISAAC III data was collected in Cape Town in 2002 and Polokwane in 2004-2005 where adolescents were also included.
According to Masekela, the latest study collecting data on asthma was the Global Asthma Network (GAN) Phase one study, to which the Cape Town centre contributed. Masekela says the data from the ISAAC studies – ISAAC 1 and ISAAC 3 as well as GAN is available in South Africa only for Cape Town.
This means that it is possible to compare trends in childhood asthma in Cape Town over a longer time period, and data from ISAAC 3 can be used to compare Polokwane and Cape Town. But there isn’t current data collected by the GAN to give a clear picture of childhood asthma in the other cities and provinces.
In the 2022 Global Asthma report changes among the prevalence of asthma symptoms – measured as a 12-month prevalence rate of wheezing among adolescents aged 13 to14 – showed that in ISAAC 1, 16% of the around 5 000 adolescents surveyed in Cape Town had symptoms, which increased to 20.3% of just over 5 000 surveys in ISAAC 3 and finally 21.7% of the just under 4 000 adolescents surveyed for the 2022 study.
Masekela says in Cape Town if we look at the period between ISAAC Phase 1 and phase three, there was an increase in the prevalence [of asthma in children], but from the ISAAC 3 to the GAN Phase 1, there has been a stabilisation in the asthma prevalence [among children. “So, it’s very high, it’s over 20%, but it’s stable so it hasn’t been increasing, which it was doing before.”
When comparing data from Polokwane and Cape Town in ISAAC 3, at the time of the study, more children and adolescents in Cape Town had severe asthma than in Polokwane. The prevalence of asthma in children and adolescents was also higher in Cape Town.
Situation is ‘interesting and worrying’
Masekela explains that in many low-and-middle-income countries, those living with asthma don’t have access to the right asthma medications, namely inhalers. What also happens is that when those individuals have access to asthma medications, they are only able to get the reliever inhaler, not the controller inhaler.
People living with asthma need two types of inhalers, a reliever inhaler which brings relief and opens up the chest during an asthma attack and a control medication which is used every day to reduce inflammation in the long run. In order to control asthma adequately, both inhalers need to be used and used correctly.
In South Africa, both types of inhalers are on the Essential Medicines List.
“The story of South Africa is interesting and worrying. We have in our essential medicine list inhalers [both relievers and controllers],” she says. “It should be available. It’s on the essential medicine list for the primary care level. So any person who has asthma in South Africa should have access to that first step of treatments.”
Yet the data from South Africa suggests there is a problem. When looking at the symptoms of asthma among schoolchildren from the GAN phase one study, Masekela says it is worrying because they found that many children in South Africa with asthma symptoms don’t have an asthma diagnosis and of those that do have the diagnosis most only have the reliever inhaler and very few are using both the reliever and the controller inhaler.
“We know that asthma is under-diagnosed and actually the data from Cape Town, as well as Durban, is very similar. You see that 50% of adolescents have severe symptoms, half of them have never got the label – they’ve never been diagnosed as having asthma,” she says.
Under-diagnosed
A possible reason for the under-diagnosis, according to Masekela, is that when a child presents to a clinic with wheezing, the child is treated for something else that might be causing the symptoms and sent home. Then when the child goes back a few weeks or months later with the same symptoms, they are seen by a different doctor or nurse and there isn’t continuity, so the fact that the symptoms are recurrent isn’t picked up on.
Manjra tells Spotlight that asthma can sometimes be difficult to diagnose in small children because its symptoms – wheezing, shortness of breath, tight chest, and coughing – can be caused by a number of other diseases. Wheezing, in particular, can be caused by a number of conditions that can affect children.
“The most common being viral upper respiratory tract infection, particularly with RSV [respiratory syncytial virus] and rhinovirus. And sometimes in young children, it can be extremely difficult to make a correct diagnosis of asthma because there’s overlap between viral-induced wheezing and asthma,” he says.
“However, if the child has an underlying – what we call atopic predisposition – that means if the child has eczema or has allergic rhinitis or food allergy or has [an] inhalant allergy, then the possibility of that child having asthma is very high,” he says.
Other childhood conditions that can cause wheezing in children are TB and inhaling foreign bodies into the lungs.
“So, the diagnosis of asthma in young children is basically made by an exclusion of other causes of wheezing,” he says. “Asthma diagnosis is made over a period of time because, as I’ve mentioned, it’s recurrent wheezing.”
Another problem, according to Masekela, is that those people who do receive a diagnosis of asthma are often not getting the right treatment.
“People who have a label at least should have access to the treatments, but we do see that even in those that have the diagnosis, a lot of them are not using their medicine because they’re getting repeated attacks, they have severe symptoms,” she says. “So, something is not right. Either they are not getting the label, we know that’s happening, or they’re not getting the right treatment.”
This is a bi-directional problem, Masekela says, in that either healthcare workers are not adequately teaching patients how to use both inhalers or patients are relying on the reliever medications despite being taught how to use both.
Manjra says that while inhalers are on the EML, this doesn’t necessarily translate to healthcare facilities having stock. Meaning that there can be stock-out of the medication, but also of the spacers that children need to use with the inhalers.
According to Manjra, children are unable to use inhalers properly with spacers, because the inhaler releases the plume of medication too quickly for the child to be able to breathe it into their lungs. The spacer allows the medication to go into a holding chamber where the child is able to breathe the medication into their lungs in a controlled way, through a special valve.
Better education needed
The solution to the problems of the under-diagnosis of asthma and incorrect inhaler use is better education on all fronts, says Masekela. There needs to be better training among healthcare workers on how to recognise asthma, how to manage it and how to teach patients how to manage it properly.
“We know that there is a system problem about them [children] getting the correct medication, using the correct medication and that all boils down to education of the patient, education of the health workers. And really, overall education in the community about how to handle asthma,” she says.
She adds that patients and the wider community also need to be educated on what asthma is and how to manage it properly and destigmatise it. A good starting place is in schools so that children who are living with asthma and their peers are able to better understand the condition and be more accepting of the use of inhalers.
“It’s important that we then find strategies to get people to understand the need for using these medicines, even when they’re feeling well,” she says.
A study of 104 children wearing pedometers to monitor daily activity showed that higher levels of physical activity are associated with reduced susceptibility to upper respiratory tract infections such as the common cold. Reporting the findings in Pediatric Research, the researchers suggest reduced inflammatory cytokines and improved immune responses as a possible mechanism.
Wojciech Feleszko, Katarzyna Ostrzyżek-Przeździecka and colleagues measured the physical activity levels and symptoms of upper respiratory tract infections of children aged between four and seven years in the Warsaw city region between 2018 and 2019. Participants wore a pedometer armband 24 hours a day for 40 days to measure their activity levels and sleep duration. For 60 days, parents used daily questionnaires to report their children’s symptoms of upper respiratory tract infections, such as coughing or sneezing. On a second questionnaire, parents reported their children’s vaccinations, participation in sport, whether they had siblings, and their exposure to smoking and pet hair.
The authors found that as the average daily number of steps taken by children throughout the study period increased by 1000, the number of days that they experienced symptoms of upper respiratory tract infections decreased by an average of 4.1 days. Additionally, children participating in three or more hours of sport per week tended to experience fewer days with respiratory tract infection symptoms than those not regularly participating in sports.
Higher activity levels at the beginning of the study were associated with fewer days with respiratory tract infection symptoms during the following six weeks. Among 47 children, with 5668 average daily steps during the first two weeks of the study period, the combined number of days during the following six weeks that these children experienced upper respiratory tract infection symptoms was 947. However, among 47 children whose initial average daily steps numbered 9368, the combined number of days during the following six weeks that these children experienced respiratory symptoms for was 724. Upper respiratory tract infection symptoms were not associated with sleep duration, siblings, vaccinations, or exposure to pet hair or smoking.
The authors speculate that higher physical activity levels could help reduce infection risk in children by reducing levels of inflammatory cytokines and by promoting immune responses involving T-helper cells. They also suggest that skeletal muscles could release small extracellular vesicles that modulate immune responses following exercise. However, they caution that future research is needed to investigate these potential mechanisms in children. In addition, since this was an observational study, causality could not be established.
Airway inflammation and emphysema are more common in marijuana smokers than cigarette smokers, according to a study published in Radiology. Researchers said the difference may be due to the way that marijuana is smoked, which is usually inhaled more deeply and without a filter.
Marijuana is one of the most widely used psychoactive substances in the world and the most-commonly smoked substance after tobacco. Its use has increased in recent years amid legalisation of recreational marijuana in many countries. The growing use has created an urgent need for information on marijuana’s effects on the lungs, something that is currently lacking.
“We know what cigarettes do to the lungs,” said study author Giselle Revah, MD, a cardiothoracic radiologist and assistant professor at the University of Ottawa. “There are well researched and established findings of cigarette smoking on the lungs. Marijuana we know very little about.”
To find out more, Dr Revah and colleagues compared chest CT results from 56 marijuana smokers with those of 57 non-smoking controls and 33 tobacco-only smokers.
Pulmonary emphysema in (A, B) marijuana and (C, D) tobacco smokers. (A) Axial and (B) coronal CT images in a 44-year-old male marijuana smoker show paraseptal emphysema (arrowheads) in bilateral upper lobes. (C) Axial and (D) coronal CT images in a 66-year-old female tobacco smoker with centrilobular emphysema represented by areas of centrilobular lucency (arrowheads). (Murtha, et al.)
Lack of filtering partly to blame
Three-quarters of the marijuana smokers had emphysema, a lung disease that causes difficulty with breathing, compared with 67% of the tobacco-only smokers. Only 5% of the non-smokers had emphysema. Paraseptal emphysema, which damages the tiny ducts that connect to the air sacs in the lungs, was the predominant emphysema subtype in marijuana smokers compared to the tobacco-only group.
Airway inflammation was also more common in marijuana smokers than non-smokers and tobacco-only smokers, as was gynecomastia, enlarged male breast tissue due to a hormone imbalance. Gynecomastia was found in 38% of the marijuana smokers, compared with 11% of the tobacco-only smokers and 16% of the controls.
The researchers found similar results among age-matched subgroups, where the rates of emphysema and airway inflammation were again higher in the marijuana smokers than the tobacco-only smokers.
There was no difference in coronary artery calcification between age-matched marijuana and tobacco-only groups.
Dr. Revah said the results were surprising, especially considering that the patients in the tobacco-only group had an extensive smoking history.
“The fact that our marijuana smokers – some of whom also smoked tobacco – had additional findings of airway inflammation/chronic bronchitis suggests that marijuana has additional synergistic effects on the lungs above tobacco,” she said. “In addition, our results were still significant when we compared the non-age-matched groups, including younger patients who smoked marijuana and who presumably had less lifetime exposure to cigarette smoke.”
The reasons for the differences between the two groups is likely due to several factors. Marijuana is smoked unfiltered, Dr Revah noted, while tobacco cigarettes are usually filtered. This results in more particulates reaching the airways from smoking marijuana.
In addition, marijuana is inhaled with a longer breath hold and puff volume than tobacco smoke.
“It has been suggested that smoking a marijuana joint deposits four times more particulates in the lung than an average tobacco cigarette,” Dr Revah said. “These particulates are likely airway irritants.”
The higher incidence of emphysema may also be due to the way that marijuana is smoked. Full inhalation with a sustained Valsalva manoeuvre, an attempt at exhalation against a closed airway, may lead to trauma and peripheral airspace changes.
More research is needed, Dr Revah said, with larger groups of people and more data on how much and how often people are smoking. Future research could also look at the impact of different inhalation techniques, such as through a bong, a joint or a pipe.
“It would be interesting to see if the inhalation method makes a difference,” Dr Revah said.
In pulmonary medicine, it has long been debated as to whether ventilator overstretches lung tissue, and now new research published in the American Journal of Respiratory and Critical Care Medicine has proven that they do in fact cause overstretching.
The University of California Riverside researchers showed that there were major differences between natural breathing versus the forced breathing from ventilators. These results are critical, particularly in context of the COVID pandemic and the rush to build ventilators.
“Using novel techniques, we observed that ventilators can overextend certain regions of the lungs,” said Mona Eskandari, assistant professor of mechanical engineering, who led the research. These results may explain why lung health declines for patients the longer they spend on the machines, especially in the case of disease.
Eskandari’s bMECH lab pioneered a technique to study lungs as they are made to breathe. On a custom-built ventilator designed in their lab, the researchers imitated both natural and artificial breathing. Then, they observed isolated lungs involved in both types of breathing using multiple cameras collecting fast, high-resolution images, a method called digital image correlation.
“Our setup allows us to imitate both physiological and artificial breathing on the same lung with the switch of a button,” Eskandari said. “The unique combination of our ventilator with digital image correlation gives us unprecedented insights into the way specific regions of the lungs work in concert with the whole.”
Using their innovative method to interface these two systems, UCR researchers collected evidence demonstrating that natural breathing stretches certain parts of the lung as little as 25% while those same regions stretch to as much as 60% when on a ventilator.
Scholars traditionally model the lungs like balloons, or what they refer to as thin-walled pressure vessels, where pushing air in and pulling air out are understood to be mechanically equivalent.
To explain what they observed in this study, the researchers propose moving away from thin-walled pressure vessel models and instead towards thick-walled models. Unlike thin-walled pressure vessels theory, a thick-walled model accounts for the differing levels of stress in airways resulting from ventilators pushing air in versus natural breathing, which pulls air in. This helps to explain how airways are more engaged and air is more evenly distributed in the lung during physiological breathing.
Iron lungs, the gigantic ventilators used during the late 1940s polio outbreak, acted more like a human chest cavity, expanding the lung as it naturally would. This creates a vacuum effect that pulls air into the lungs. Though this action is gentler for the lungs, these bulky systems prevented easy access to monitoring other organs in hospital care.
By contrast, modern ventilators are more portable and easier for caretakers to work with. However, they push air into the lungs that is not evenly distributed, overstretching some parts and causing a decline in lung health over time.
While it is unlikely that hospitals will return to the iron lung models, it is possible that modern machines can be altered to reduce injury.
“Now that we know about excessive strain when air is delivered to the lungs, the question for us becomes about how we can improve ventilation strategies by emulating natural breathing,” Eskandari said.
In a world first, scientists have witnessed the fusion two viruses, influenza A virus (IAV) and respiratory syncytial virus (RSV), forming a single, hybrid virus particle (HVP). The discovery was published in Nature Microbiology.
Viruses often share tropism for the same system, such as respiratory viruses preferentially infecting the respiratory system. Coinfections by more than one virus represent between ~10–30% of all respiratory viral infections and are common among children. The clinical impact of viral coinfections is unclear: while some studies indicate that coinfections do not alter the outcome of disease, others report increased incidence of viral pneumonia.
Though evidence suggests virus–virus interactions play an important role in virus dynamics and transmission, viruses are typically studied in isolation. Recent work showed that interactions among respiratory viruses occur and have impacts at multiple levels, from populations, to individuals and tissues. However, studies characterising direct virus–virus interactions within cells are scarce. Here we report previously unknown interactions between IAV and RSV, two clinically important respiratory viruses that belong to different taxonomical families.
To investigate virus–virus interactions, the researchers infected human lung cells with both influenza A virus (IAV) and respiratory syncytial virus (RSV). Using super-resolution microscopy, live-cell imaging, scanning electron microscopy and cryo-electron tomography, the researchers found extracellular and membrane-associated filamentous structures consistent with hybrid viral particles (HVPs).
The researchers found that HVPs harbour surface glycoproteins and ribonucleoproteins of IAV and RSV. HVPs use the RSV fusion glycoprotein to evade anti-IAV neutralising antibodies and infect and spread among cells lacking IAV receptors. Finally, we show that IAV and RSV coinfection in primary cells of the bronchial epithelium results in viral proteins from both viruses latching on together at the apical cell surface.
“Our observations define a previously unknown interaction between respiratory viruses that might affect virus pathogenesis by expanding virus tropism and enabling immune evasion,” the researchers wrote.
“This kind of hybrid virus has never been described before,” virologist and senior author Pablo Murcia toldThe Guardian. “We are talking about viruses from two completely different families combining together with the genomes and the external proteins of both viruses. It is a new type of virus pathogen.”
When IAV and RSV coinfect, IAV becomes more infectious, infecting a wider array of human cells. Carrying the RSV surface proteins, IAV was able to better evade the immune system. The HVP also spread into cells lacking influenza receptors, letting it progress further down the respiratory tract.
The relationship is not mutually beneficial for the viruses as RSV loses potency. Overall though, pilfering another virus’s tools could play a role in viral pneumonia.
“RSV tends to go lower down into the lung than the seasonal flu virus, and you’re more likely to get more severe disease the further down the infection goes,” said Dr Stephen Griffin, a virologist at the University of Leeds who was not involved in the study.
“It is another reason to avoid getting infected with multiple viruses, because this [hybridisation] is likely to happen all the more if we don’t take precautions to protect our health,” he added.
The researchers also found that the combination of viruses was important; IAV did not form an effective hybrid with rhinovirus.
People with fibrotic interstitial lung disease that has no obvious cause are more likely to die if they live in areas with higher levels of air pollution composed of chemicals associated with industrial sources and vehicular traffic, according to new published today in JAMA Internal Medicine.
The University of Pittsburgh study is the first to link the chemical composition of fine particulate air pollution to worsened fibrotic interstitial lung disease (fILD) outcomes. It is also the largest study ever done to evaluate the impact of air pollution on these patients.
“Some people with these lung diseases have an expected lifespan from diagnosis to death of only a few years, and yet it’s a mystery as to why they developed the disease, why their lungs become so scarred,” said lead author Gillian Goobie, MD, doctoral candidate. “Our study points to air pollution – specifically pollutants from factories and vehicles – as potentially driving faster disease progression and premature death in these patients.”
Goobie and her team obtained data from 6,683 patients with fILDs in the U.S. and Canada and linked their home addresses with satellite and ground-monitoring air pollution data to determine air pollutant composition to an accuracy of less than half a mile.
The team specifically looked at a pollutant known as PM2.5, which refers to particulate matter that measures less than 2.5 microns across, a size invisible to the naked eye. This type of pollution is so small that it can infiltrate deep into the lungs and even cross into the blood stream, where it can contribute to other diseases outside of the lungs, such as heart disease.
“In the past, most environmental health research has focused on the simple definition of PM2.5 as anything of that size,” said co-author James Fabisiak, Ph.D., associate professor in Pitt Public Health’s Department of Environmental and Occupational Health. “But PM2.5 is chemically diverse, with a different composition depending on whether it came from a forest fire or a tailpipe. Research has lacked in determining if the type of PM2.5 matters when it comes to health effects. Our new research is a big step toward filling in that knowledge gap.”
The team found that increasing levels of PM2.5 were linked to more severe disease at diagnosis, faster disease progression as measured by lung function decline and higher likelihood of dying sooner. Pollution high in sulfate (typically produced by factories, such as the coal and steel industries), nitrate (primarily from fossil fuel combustion) and ammonium (usually produced by industry or agriculture) were associated with worse outcomes, whereas chemical signatures from more naturally occurring particulate matter such as sea salt or soil dust didn’t carry as high of an association.
After pollution leaves a smokestack or tailpipe, Goobie noted that sulfate- and nitrate-containing aerosols can be formed in the atmosphere from those and other gaseous pollutants and can be acidic, which can be very damaging to the tiny air sacs of the lungs.
The team is now doing laboratory studies looking at the impact of these pollutants on lung cells at the molecular level to better understand why they are particularly damaging to the lungs of certain people and whether exposure to the pollutants triggers changes to how certain genes work that could cause runaway scarring.
According to the team’s calculations, if exposure to industrial pollutants hadn’t occurred, most premature deaths among participants living in areas of North America with a heavier burden of industry could have been avoided. Participants of colour were disproportionately exposed to higher levels of human-made air pollutants: 13% of the high-exposure group were non-white, but only 8% of the low-exposure group, highlighting the impact of environmental injustice in these findings as well.
Co-senior author S. Mehdi Nouraie, MD, PhD, associate professor of pulmonary, allergy and critical care medicine at Pitt’s School of Medicine, said that the findings further emphasise the need for people with lung conditions that make them more vulnerable to pollution to pay attention to the air quality index and consider minimising time outdoors or in rooms without good air filtration during poor air quality days.
“Ultimately, we want to encourage a data-driven awareness,” A/Prof Nouraie said. “We want people to think about the quality of the air we breathe. Patients, health care providers and policymakers can all use the new information we’re providing to try to improve health outcomes. When you make the air safe for the most vulnerable to breathe, you’re making it safe for all of us.”
Blocking calcium signalling in immune cells suppresses allergic asthma, but without compromising the immune defence against flu viruses, according to the findings of a new study published in Science Advances.
The researchers showed that, in a mouse model, removing the gene for a certain calcium channel reduced asthmatic lung inflammation caused by house dust mite faeces, a common cause of allergic asthma. Blocking signals sent through this channel, the calcium release-activated calcium (CRAC) channel, with an investigational inhibitor drug had a similar effect.
The study revolved human cells’ use of signalling and switch-flipping ions, mainly calcium. When triggered by viral proteins or allergens, T cells open channels in their outer membranes, allowing calcium in to activate signalling pathways that control cell division and secretion of cytokine molecules.
Past work had found that CRAC channels in T cells regulate their ability to multiply into armies of cells designed to fight infections caused by viruses and other pathogens.
The new study showed that the CRAC channel inhibitor reduced allergic asthma and mucus build-up in mice without undermining their immune system’s ability to fight influenza, a main worry of researchers seeking to tailor immune-suppressing drugs for several applications.
“Our study provides evidence that a new class of drugs that target CRAC channels can be used safely to counter allergic asthma without creating vulnerability to infections,” said senior study author Stefan Feske, MD, a professor at NYU Langone Health. “Systemic application of a CRAC channel blocker specifically suppressed airway inflammation in response to allergen exposure.”
Allergic asthma, which is the most common form of the disease, is characterised by increased type 2 (T2) inflammation, which involves T helper (Th) 2 cells, the study authors noted. Th2 cells produce cytokines that play important roles in both normal immune defences, and in disease-causing inflammation that occurs in the wrong place and amount. In allergic asthma, cytokines promote the production of IgE antibodies and the recruitment to the lungs of inflammation-causing immune cells called eosinophils, the hallmarks of the disease.
In the new study, the research team found that deletion of the ORAI1 protein in T cells, which makes up the CRAC channel, or treating mice with the CRAC channel inhibitor CM4620, thoroughly suppressed Th2-driven airway inflammation in response to house dust mite allergens.
Treatment with CM4620 significantly reduced airway inflammation when compared to an inactive control substance, with the treated mice also showing much lower levels of Th2 cytokines and related gene expression. Without calcium entering through CRAC channels, T cells are unable to become Th2 cells and produce the cytokines that cause allergic asthma, the authors say.
Conversely, ORAI1 gene deletion, or interfering with CRAC channel function in T cells via the study drug, did not hinder T cell-driven antiviral immunity, as lung inflammation and immune responses were similar in mice with and without ORAI1.
“Our work demonstrates that Th2 cell-mediated airway inflammation is more dependent on CRAC channels than T cell-mediated antiviral immunity in the lung,” said study co-first author Yin-Hu Wang, PhD. “This suggests CRAC channel inhibition as a promising, potential future treatment approach for allergic airway disease.”
Children are more likely to develop asthma if their father was exposed to secondhand smoke when he was a child, according to a study published today in the European Respiratory Journal. The researchers also found that the children have an even higher asthma risk if their father was exposed to secondhand smoke and then also became a smoker.
The researchers say their findings highlight how smoking can cause intergenerational harm, impacting even grandchildren.
The research drew on on data from the Tasmanian Longitudinal Health Study (TAHS). TAHS began in 1968 and is one of the world’s largest and longest ongoing respiratory studies.
For this study, researchers looked at 1689 children who grew up in Tasmania, and their fathers and their paternal grandparents. They compared data on whether the children had developed asthma by age 7 with data on whether the fathers grew up with parents who smoked when they were under age 15. They also included data on whether the fathers were current or former smokers.
First author Mr Jiacheng Liu said, “We found that the risk of non-allergic asthma in children increases by 59% if their fathers were exposed to secondhand smoke in childhood, compared to children whose fathers were not exposed. The risk was even higher, at 72%, if the fathers were exposed to secondhand smoke and went on to smoke themselves.”
Researcher Dr Dinh Bui said, “Our findings show how the damage caused by smoking can have an impact not only on smokers, but also their children and grandchildren. For men who were exposed to secondhand smoke as children, our study suggests that they can still lower the risk they pass on to their own children, if they avoid smoking.”
Senior author Professor Shyamali Dharmage said, “We can’t be certain of how this damage is passed on through generations, but we think it may be to do with epigenetic changes. This is where factors in our environment, such as tobacco smoke, interact with our genes to modify their expression. These changes can be inherited but may be partially reversible for each generation.
“It’s possible that tobacco smoke is creating epigenetic changes in the cells that will go on to produce sperm when boys grow up. These changes can then be passed on to their children.”
The researchers will now investigate if the increased risk of asthma persists into adult life and whether fathers who were exposed to secondhand smoke as children pass on any increase in allergies or other lung diseases to their children.
Schematic diagram of the alveolar chip (upper left), photograph of the chip (upper middle), CAD drawing of the multi-generation alveolar structure (upper right), and two typical flow patterns in the alveolar chip (bottom). CREDIT: Yonggang Zhu
Understanding how air and particulates through the alveoli is important to better treat respiratory disease. In Biomicrofluidics, researchers detail a model alveolar system that they built to mimic the breathing action of the human lung and allows visualisation of flow patterns within the alveoli. They observed that flow changes after the 20th branching of the alveoli.
The scientists, from Harbin Institute of Technology in China, designed a chip that includes tubes arranged like the structure of a bifurcation point in the bronchial network. The upper layer of the chip is made of a flexible polymer moulded into small tubes that mimic the alveolar structure. The lower layer is glass, which allows the authors to visualise fluid flow through the tubes.
To mimic inhalation and exhalation, the scientists devised a system in which gas was pressurised in a sinusoidal fashion and pumped around the flexible tubes. Small red polystyrene spheres were added to the fluid flowing through tubes. These spheres allowed them to photograph movement of the fluid as it was pushed through the tubes by the artificial breathing apparatus.
Subsequent branches in the bronchial network are termed ‘generations’, and the team found different flow patterns for different generations. In the human lung, alveoli appear at the 15th generation and remain present for generations up to 23. The researchers found a change in flow pattern between the 19th–20th and the 21st–22nd generations.
“The alveolar flow pattern of the 19th generation is dominated by vortex flow,” author Yonggang Zhu said. “Alveolar flow patterns in the 20th generation are similar to those in the 19th, but somewhat compressed.”
The investigators observed a change in the next generation.
“The alveolar flow pattern in the 21st generation has both vortex flow and radial flow. The vortex region is much smaller than the radial flow region. By the time the flow reaches the 22nd generation, vortex flow disappears completely, and we observe only radial flow,” Zhu said.
The authors also found evidence of chaotic behaviour near the vortex centre. They said more research is needed to fully understand this, but they felt the current study provides a good baseline for deeper investigations.
With the model, researchers will be able to study changes in flow patterns in the alveoli due to diseases such as emphysema and COPD.
