Treatment of lung diseases via nanoparticles and nanorobots: Are these viable alternatives to overcome current treatments?

Researchers Discover The Lungs Communicate Directly With The Brain To ...

University of Calgary researchers have discovered the lungs communicate directly with the brain when there is an infection. Findings show the brain plays a critical role in triggering the symptoms of sickness, which may change the way we treat respiratory infections and chronic conditions.

The lungs are using the same sensors and neurons in the pain pathway to let the brain know there's an infection. The brain prompts the symptoms associated with sickness; that overall feeling of being unwell, feeling tired and loosing your appetite. The discovery indicates we may have to treat the nervous system as well as the infection."

Dr. Bryan Yipp, MD '05, MSc'05, clinician researcher at the Cumming School of Medicine and senior author on the study

Prior to this study, conducted in mice, it was thought infections in the lungs and pneumonia induce inflammatory molecules that eventually made their way to the brain through the blood stream. Sickness was thought to be a consequence of the immune system kicking into action. However, findings reveal that sickness results from nervous system activation in the lung.

Understanding the lung-brain dialogue is important for treatment because bacteria that cause lung infections can produce a biofilm, a coating to surround themselves so the nervous system can't see them. That allows the bug to hide out in the lungs for a long time, which may shed light across diverse serious lung infections that are less symptomatic. For example, an unexplained anomaly Yipp witnessed in the intensive care unit (ICU) during COVID. The phenomenon, coined "happy hypoxia", was being recorded in ICUs throughout the world.

"We would have patients whose oxygen levels were extremely low and x-rays confirmed they may need to be put on life support. Yet, when I went to see the patient, they would say I feel fine," says Yipp. "These people were experiencing limited sickness symptoms even though the virus was aggressively damaging their lungs."

Yipp says understanding the lung brain communication pathways may also have broad implications for people with chronic lung infections like cystic fibrosis (CF). Many people with CF have a biofilm bacterium in their lungs and are asymptomatic. They feel okay, but then have a flare where they can become very ill. The reason for the flare can't always be traced.

"It is possible the flare is also neurological that these people live asymptomatically because bacteria are hiding out," says Yipp.

The findings, published in Cell, are the work of an interdisciplinary team including experts in neurobiology, microbiology, immunology, and infectious disease.

"Physician specialties are usually based on individual organs, with pulmonologists caring for the lungs and neurologists caring for the brain. Our study shows the lung is altering the brain and the brain is altering the organ. This intersection of communication is a different way of thinking about disease," says Yipp. "It's all connected to the brain and there are probably even more complex circuits that are happening. We can now think about targeting neurocircuitry along with antibiotics to deal with infections and the sickness they cause."

University of Calgary researchers Drs. Christophe Altier, PhD, Joe Harrison, PhD, and Deborah Kurrasch, PhD, along with Dr. Jaideep Bains, PhD, Krembil Research Institute, Toronto, are corresponding authors on the study.

The researchers add there was one more unique finding. Male mice were much sicker than the females even though they had the same bacterial infection. Researchers found that male sickness was more dependent on neuronal communications then females. Yipp says this finding could lend credibility to the so-called "man flu", a colloquial term where men are thought to wildly exaggerate sickness due to respiratory infections. Turns out they may not be exaggerating, after all. 

University of Calgary researchers have discovered the lungs communicate directly with the brain when there is an infection. Findings show the brain plays a critical role in triggering the symptoms of sickness, which may change the way we treat respiratory infections and chronic conditions.

"The lungs are using the same sensors and neurons in the pain pathway to let the brain know there's an infection," says Dr. Bryan Yipp, MD '05, MSc'05, clinician researcher at the Cumming School of Medicine and senior author on the study. "The brain prompts the symptoms associated with sickness; that overall feeling of being unwell, feeling tired and loosing your appetite. The discovery indicates we may have to treat the nervous system as well as the infection."

Prior to this study, conducted in mice, it was thought infections in the lungs and pneumonia induce inflammatory molecules that eventually made their way to the brain through the blood stream. Sickness was thought to be a consequence of the immune system kicking into action. However, findings reveal that sickness results from nervous system activation in the lung.

Understanding the lung-brain dialogue is important for treatment because bacteria that cause lung infections can produce a biofilm, a coating to surround themselves so the nervous system can't see them. That allows the bug to hide out in the lungs for a long time, which may shed light across diverse serious lung infections that are less symptomatic. For example, an unexplained anomaly Yipp witnessed in the intensive care unit (ICU) during COVID. The phenomenon, coined "happy hypoxia", was being recorded in ICUs throughout the world.

"We would have patients whose oxygen levels were extremely low and x-rays confirmed they may need to be put on life support. Yet, when I went to see the patient, they would say I feel fine," says Yipp. "These people were experiencing limited sickness symptoms even though the virus was aggressively damaging their lungs."

Yipp says understanding the lung brain communication pathways may also have broad implications for people with chronic lung infections like cystic fibrosis (CF). Many people with CF have a biofilm bacterium in their lungs and are asymptomatic. They feel okay, but then have a flare where they can become very ill. The reason for the flare can't always be traced.

"It is possible the flare is also neurological that these people live asymptomatically because bacteria are hiding out," says Yipp.

The findings, published in Cell, are the work of an interdisciplinary team including experts in neurobiology, microbiology, immunology, and infectious disease.

"Physician specialties are usually based on individual organs, with pulmonologists caring for the lungs and neurologists caring for the brain. Our study shows the lung is altering the brain and the brain is altering the organ. This intersection of communication is a different way of thinking about disease," says Yipp. "It's all connected to the brain and there are probably even more complex circuits that are happening. We can now think about targeting neurocircuitry along with antibiotics to deal with infections and the sickness they cause."

University of Calgary researchers Drs. Christophe Altier, PhD, Joe Harrison, PhD, and Deborah Kurrasch, PhD, along with Dr. Jaideep Bains, PhD, Krembil Research Institute, Toronto, are corresponding authors on the study.

The researchers add there was one more unique finding. Male mice were much sicker than the females even though they had the same bacterial infection. Researchers found that male sickness was more dependent on neuronal communications then females. Yipp says this finding could lend credibility to the so-called "man flu", a colloquial term where men are thought to wildly exaggerate sickness due to respiratory infections. Turns out they may not be exaggerating, after all. 

Source:

Journal reference:

Granton, E., et al. (2024) Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection. Cell. Doi.Org/10.1016/j.Cell.2024.03.001.

New Insights Into The Link Between Respiratory Infections And Chronic ...

A 3D reconstruction of a mouse lung four days after infection with fluorescent Sendai virus reveals widespread virus presence (red) and active replication (green). A study by researchers at WashU Medicine shows that respiratory viruses can hide out in immune cells in the lungs long after the initial symptoms of an infection have resolved, creating a persistently inflammatory environment that promotes the development of chronic lung diseases such as asthma.

Doctors have long known that children who become seriously ill with certain respiratory viruses such as respiratory syncytial virus (RSV) are at elevated risk of developing asthma later in life. What they haven't known is why.

A new study by researchers at Washington University School of Medicine in St. Louis may have solved the mystery. The study, in mice, shows that respiratory viruses can hide out in immune cells in the lungs long after the initial symptoms of an infection have resolved, creating a persistently inflammatory environment that promotes the development of lung disease. Further, they showed that eliminating the infected cells reduces signs of chronic lung damage before they progress to a full-blown chronic respiratory illness.

The findings, published Oct. 2 in Nature Microbiology, point to a potential new approach to preventing asthma, chronic obstructive pulmonary disease (COPD) and other chronic lung diseases by eradicating the persistent respiratory viruses that fuel these conditions.

"Right now, children who have been hospitalized for a respiratory infection such as RSV are sent home once their symptoms resolve," said senior author Carolina B. López, PhD, a professor of molecular microbiology and a BJC Investigator at WashU Medicine.

To reduce the risk that these children will go on to develop asthma, maybe in the future we will be able to check if all of the virus is truly gone from the lung, and eliminate all lingering virus, before we send them home."

Carolina B. López, Professor, Molecular Microbiology, Washington University School of Medicine

About 27 million people in the U.S. Are living with asthma. Many factors influence a person's likelihood of developing the chronic breathing illness, including living in a neighborhood with poor air quality, having exposure to cigarette smoke and being hospitalized for viral pneumonia or bronchitis while young. Some researchers — López included — suspected that the link between serious lung infection and subsequent asthma diagnosis was due to lingering virus in the lungs that causes ongoing damage, but a direct link between the ongoing presence of virus and chronic lung disease has not been previously shown.

López and first author Ítalo Araújo Castro, PhD, a postdoctoral researcher in her lab, developed a unique system involving a natural mouse virus known as Sendai virus, and fluorescent markers of infection. Sendai is related to human parainfluenza virus, a common respiratory virus that, like RSV, has been linked to asthma in children. Sendai behaves in mice in very much the same way that human parainfluenza virus behaves in people, making it an excellent model of the kinds of infections that could lead to chronic lung disease.

Using the fluorescent trackers, the researchers could observe signs of the virus throughout infection. After about two weeks, the mice recovered, but viral RNA and protein were still detectable several weeks later in their lungs, hidden away in immune cells.

"Finding persistent virus in immune cells was unexpected," López said. "I think that's why it had been missed before. Everyone had been looking for viral products in the epithelial cells that line the surface of the respiratory system, because that's where these viruses primarily replicate. But they were in the immune cells."

Moreover, the presence of the virus changed the behavior of the infected immune cells, causing them to become more inflammatory than the uninfected immune cells. Persistent inflammation sets the stage for chronic lung disease to arise, the researchers said. Indeed, seven weeks after infection, the mice's lungs exhibited inflammation of air sacs and blood vessels, abnormal development of lung cells and excess immune tissue — all signs of chronic inflammatory lung damage, even though the mice appeared outwardly to have recovered. Once the infected immune cells were eliminated, the signs of damage diminished.

"We use a perfectly matched virus-host pairing to prove that a common respiratory virus can be maintained in immunocompetent hosts for way longer than the acute phase of the infection, and that this viral persistence can result in chronic lung conditions," Castro said. "Probably the long-term health effects we see in people who are supposed to be recovered from an acute infection are actually due to persistence of virus in their lungs."

The findings point to new ways to think about preventing chronic lung diseases, the researchers said.

"Pretty much every single child gets infected with these viruses before the age of 3, and maybe 5% get serious enough disease that they could potentially develop persistent infection," López said. "We're not going to be able to prevent children from getting infected in the first place. But if we understand how these viruses persist and the effects that persistence has on the lungs, we may be able to reduce the risk of serious long-term problems."

Pneumonia In Children: Causes, Symptoms, Diagnosis, And More

Pneumonia is a lung infection that can lead to serious complications in children. The illness may present differently in children than it does in adults.

Pneumonia is an infection of the lungs caused by bacteria, viruses, or fungi. It is marked by inflammation in the air sacs of one or both lungs. The sacs, also called alveoli, fill with fluid or pus and may lead to fever, cough, or trouble breathing.

While these symptoms are classic in adults, children may present with different symptoms or seemingly unrelated symptoms.

Here's what pneumonia looks like in kids, what causes it, and how it can be treated.

Babies and toddlers with pneumonia may experience:

Another way to recognize pneumonia in a child is by observing their breathing. Children with pneumonia may exhibit something called intercostal retractions. During retractions, the skin between their ribs pulls in with each breath or their nostrils may flare.

Your child may also breathe faster than usual and make groaning sounds while breathing.

Seek immediate medical care

Seek medical care if your child shows symptoms that concern you.

Babies 6 months old and younger may need hospital treatment for pneumonia.

Warning signs that your older child needs immediate medical help include:

rapid breathing (more than 20 breaths per minute for kids, 40 for toddlers, or 50 for babies)

having seizures

becoming lethargic or unresponsive

Bacterial pneumonia is caused by different strains of bacteria, including pneumococcal bacteria, Haemophilus influenzae bacteria, streptococcal bacteria, or intestinal bacteria.

Pneumonia caused by bacteria is more more common in older kids and adolescents, kids who have underlying health issues, and very young infants who have been exposed to certain bacteria during birth.

What is walking pneumonia?

This type of pneumonia is typically mild, may not cause serious symptoms that slow a child down (hence the term "walking"), and generally does not lead to hospitalization.

To diagnose pneumonia, your child's doctor will perform a physical exam and review the symptoms they have been experiencing.

Treatment for pneumonia in children depends on the underlying cause. Viral pneumonia often resolves on its own without medical treatment. Bacterial pneumonia, on the other hand, may require prescription antibiotics to effectively clear.

One main way to prevent pneumonia is to stay up-to-date on vaccines. Getting these vaccines can help protect your child from infections that can lead to pneumonia.

Vaccines that may help prevent pneumonia include:

Pneumococcal vaccination: The Centers for Disease Control and Prevention (CDC) recommends pneumococcal vaccination for children younger than 5 years, adults 65 years or older, and children and adults at increased risk for pneumococcal pneumonia, the most common, severe type of pneumococcal disease. Ask your child's healthcare professional about this series of vaccinations.

Seasonal influenza: The CDC recommends a flu vaccine for all children 6 months of age and older, and children 6 months old through 8 months of age may need two doses of flu vaccine in one flu season.

Respiratory syncytial virus (RSV): The CDC recommends one of two options to protect infants from severe RSV. Either an individual can get a maternal RSV vaccine (Pfizer's Abrysvo) during pregnancy, or infants whose mothers did not get an RSV vaccine during pregnancy need to get an RSV antibody after birth.

COVID-19: COVID-19 and the virus that causes it are common causes of pneumonia. The CDC recommends children 6 months and older have a COVID-19 vaccination.

Other ways to help protect your child from getting pneumonia include good hygiene — washing your hands often when around your child, good indoor air quality — avoiding exposure to smoke, and helping them have adequate nutrition and sleep.

The outlook for most children with pneumonia is good. Again, viral pneumonia tends to resolve on its own without treatment. Likewise, most children do not experience any long-term lung issues.

Pneumonia can be very serious, especially in children with limited access to effective medical care. Worldwide, around 1.3 million children die each year from pneumonia and related complications.

If your child is immunocompromised or has other chronic health issues, speak with your pediatrician about the pneumococcal vaccine.

---