Asthma chronic

Columbia researchers have found why babies are susceptible to repeated bouts of common respiratory infections--but also have a unique weapon to fight off new pathogens that healthy adults lack. A pair of new studies led by researchers at Columbia University explains why babies get so many common respiratory infections and identifies a specialized cluster of immune cells found only in babies that help them better cope with new pathogens. "We know little about how the immune system develops throughout life, and most of what we know about immune system development in children comes from animal studies," says Donna Farber, PhD, an expert in immune system development at Columbia University Vagelos College of Physicians and Surgeons who led the research. "But mice develop much more quickly than humans and their immune systems are a bit different than ours." Using a trove of tissue samples from deceased pediatric organ donors, Farber's team was able to pinpoint aspects of immune system development that distinguish babies from adults. Immune cells in lungs and gut take time to mature One study, published in Immunity, found that specialized immune cells called memory T cells -- formed after first exposure to a pathogen -- accumulate rapidly in the lungs and intestines through age 3 and more gradually in blood and lymph tissues. These cells enable older children and adults to mount an immediate and specific immune response during the next encounter with a pathogen. But there's a hitch. "We found that memory T cells in young children are not functionally mature and only begin to have the capacity for protective immunity at around ages 4 to 6 years," Farber says. "This explains why babies and young children are more vulnerable to recurrent respiratory infections and other infectious diseases compared with adults." The findings also may explain why introducing foods to children during the first year of life could prevent severe food allergies. "Early memory T cells are more tolerant than mature memory cells, so they're not going to create an immune response against new foods," Farber says. 'Secret weapon' protects babies from new pathogens But while babies are highly susceptible to recurrent infections, a second study, published in Nature Immunology, found that babies have a unique way of coping with new pathogens. The researchers found clusters of antibody-producing B cells surrounded by T cells in the infants' lungs. This bronchus-associated lymphoid tissue, or BALT, is formed between 6 and 12 months of age and disappears after age 3. "BALT enables the lung to make antibodies to respiratory pathogens well before T cell memory has developed but fall apart in later childhood when they are no longer needed," says Farber. "This mechanism helps young children respond to the many different respiratory pathogens they encounter early in life." It also may explain why young kids are more resilient to new respiratory infections compared to adults -- including SARS-CoV-2. "With SARS-CoV-2, a virus no one had ever encountered before, we saw that people in their 50s and 60s were very susceptible to severe COVID, but most kids exposed to SARS-CoV-2 were fine, and many didn't even have symptoms," Farber says. "That told us that the babies and young children must have some adaptations to respond to new pathogens that adults don't have." BALT also may be a reason why some children develop chronic asthma and allergies. "It's possible that these diseases may be caused in part by the abnormal persistence of BALT well into childhood, which could trigger an overreaction to certain antigens," says Farber. Farber adds that the study may provide clues about why early trials of intranasal COVID vaccines have not shown promise in adults, whereas intranasal influenza vaccine tends to work better in children. "It could be that this type of vaccine works better in children because they have BALT structures that can initiate new antibodies in the lungs." "BALT provides some protection but clearly does not protect young children from everything," Farber continues. "We have to remember that before vaccines, a third of children died of infectious diseases during infancy. So childhood vaccines are really important for protecting us."

A team of researchers has discovered that the memory of the immune system relies on characteristic epigenetic features and a specific 3D arrangement of the DNA in the nucleus of memory cells, allowing for a fast activation of these cells. These features are altered in chronic inflammation diseases like asthma and could be important in autoimmune diseases and cancer. The immune system is one of the most complex parts of our body. It keeps us healthy by getting rid of parasites, viruses or bacteria, and by destroying damaged or cancer cells. One of its most intriguing abilities is its memory: upon first contact with a foreign component (called "antigens" in scientific jargon) our adaptive immune system takes around two weeks to respond, but responses afterwards are much faster, as if the cells "remembered" the antigen. But how is this memory attained? In a recent publication, a team of researchers coordinated by Dr. Ralph Stadhouders, from Erasmus MC, and Dr. Gregoire Stik, Group Leader at the Josep Carreras Leukaemia Research Institute, provides new clues on immune memory using state-of-the-art methodologies. In their research paper, published in the scientific journal Science Immunology, the first-author Anne Onrust-van Schoonhoven and colleagues compared the response of immune cells that had never been in contact with an antigen (called naïve cells) with cells previously exposed to antigen (memory cells) and sort of knew it. They focused on the differences in the epigenetic control of the cellular machinery and the nuclear architecture of the cells, two mechanisms that could explain the quick activation pattern of memory cells. While all the cells in an individual have the same genetic information, different cell types access to different parts of the DNA. The term "epigenetics" encompasses the mechanisms that dynamically control this access. The results of the research team revealed a particular epigenetic signature in memory cells, resulting in the rapid activation of a crucial set of genes compared to naive cells. These genes were much more accessible to the cellular machinery, in particular to a family of transcription factors called AP-1. To put it into a racing context: these genes have been warming-up ever since the cell's first contact with the antigen. However, this epigenetic signature was just the tip of the iceberg. It is known that the position of the DNA in the nucleus is not random and reflects the cell's activation state. The researchers found that, indeed, the 3D distribution of DNA in the nucleus is different between naïve and memory immune cells. Key genes for the early immune response are grouped together and under the influence of the same regulatory regions, called enhancers. Keeping with the racing metaphor, the genes are not only warmed-up, but also gathered together at the starting line. Although most of the research has focused on healthy cells, the scientific team wondered whether any of the mechanisms found could, when altered, explain actual diseases in which the immune system plays an important role. To address this question, they analyzed immune cells from chronic asthma patients and found that the circuits identified as key for an early and strong immune response were overactivated. The epigenetic control of the immune system is a blossoming field and discoveries like the ones by Dr. Stik and colleagues are setting the stage for the next generation of epigenetic drugs and treatments, targeting autoimmune diseases and cancer.

Over the last several years, there has been a dramatic shift in underlying causes of advanced lung disease. Prolonged tobacco exposure from smoking, as well as occupational exposure, like what some veterans experience from spending time in war zones, are some of the factors. However, there are also new and evolving factors: the Covid-19 pandemic, for example, has left many people suffering from or vulnerable to more acute and persistent lung function issues, as well as future chronic conditions. The dramatic increase in the number of people who smoke marijuana will also create a new group of individuals likely to develop emphysema in the future. Overall, these factors point to a growing patient population in need of specialized pulmonary care in the years ahead. For patients with pulmonary conditions (including COPD, chronic asthma, emphysema, pulmonary fibrosis, bronchiectasis, cystic fibrosis, chronic bronchitis, etc.), shortness of breath can negatively impact quality of life and lead to feelings of fear and isolation. However, hospice can play a critical role in providing care and improving quality of life for those with lung disease. By helping to manage physical symptoms and emotional distress, hospice allows patients to retain their dignity and remain as comfortable as possible. Hospice clinicians are trained to provide personalized attention, such as helping patients with lung disease overcome feelings of panic that come with struggling to breathe, reducing rehospitalizations and offering peace of mind. Patients can only enjoy the benefits hospice can provide if they know about them and understand how to access them. Healthcare professionals are instrumental in educating patients about hospice and transitioning them to hospice care. Here is what they should keep in mind when caring for patients with advanced lung disease. Understanding hospice referrals There’s a lingering misperception among many patients, loved ones, and even healthcare professionals that hospice care is useful only in a patient’s last days or weeks of life. That’s just not correct – patients qualify for hospice when they have a prognosis of six months or less, and hospice care can offer comfort and support throughout those final months. Only a physician can make a clinical determination of life expectancy. However, when a patient with lung disease becomes increasingly concerned about their ability to breathe and their declining condition, both the patient and family are likely to benefit from hospice services. In most cases, there are two key characteristics that must be met to determine hospice eligibility: one is related to disease severity, and the other to ongoing disease progression. Disease severity is evidenced by shortness of breath (also known as dyspnea) while at rest or with minimal exertion and on oxygen therapy. A patient may also have unintentional weight loss and need more assistance while performing daily tasks, such as going to the bathroom or bathing. Disease progression often presents itself when disease modifying treatments are no longer effective. When that happens, we typically see increased healthcare utilization, such as hospitalizations or emergency room visits. Patients often seek help for respiratory issues, exacerbated breathing problems and/or lung infections, like bronchitis or pneumonia. Patients often say they no longer want to be hospitalized or in the ICU. Remembering that patients are eligible for hospice at “six months or less” can help prevent delays in care and unnecessary suffering for patients with advanced lung diseases. Physicians should also ask three key questions when determining when to refer a patient with advance lung disease to hospice: Is 50% or more of a patient’s waking hours spent sitting/lying down/resting? Does the patient exhibit symptoms, including cough, wheezing or shortness of breath, with minimal exertion or at rest? Does the patient require assistance with three or more basic activities of daily living (bathing, dressing, continence, ambulation, transfer or feeding)? If these questions are answered in the affirmative, the patient is experiencing functional decline, and it may be time for the clinician to consider referring the patient to hospice. What hospice provides for patients with lung disease People with lung disease often have one primary concern – “What will happen if I can’t breathe?” When a patient enrolls in hospice, the team creates an individual plan of care that details specific interventions for respiratory distress. The plan is developed with the advice and consent of the patient’s pulmonologist, respiratory therapist and hospice physician. This pre-emergency plan is designed to bring severe symptoms under control at home while giving patients and families a sense of security. The hospice team evaluates the patient’s status and updates the plan of care as symptoms and conditions change, even on a day-to-day basis. The hospice team is available around-the-clock to support patients when respiratory distress occurs. A team manager ensures that information flows between the patient’s physician, nurse, social worker, hospice aide, chaplain, volunteer and grief specialist. The team manager also helps ensure that a patient’s wishes and desires are honored. In addition, hospice coordinates and supplies all medications, medical supplies and medical equipment related to the pulmonary condition to ensure patients have everything they need. Equipment often includes oxygen, suction, nebulizer, a hospital bed, bedside commode, tray table, wheelchair and others. Hospice will commonly incorporate standard treatments, such as pulse steroids, increased oxygen and antibiotics, to help when symptoms worsen from disease exacerbation. Also, on a case-by-case basis, hospice may support high-flow oxygen, BiPAP, Airvo or Trilogy. Initiating advance care planning conversations One important way healthcare professionals can ensure patients with advanced lung disease are referred to hospice in a timely manner is to initiate advance care planning conversations well before a noticeable decline in health. According to a 2017 Kaiser Family Foundation survey, nearly 70% of Americans would prefer to die at home, if given a choice. However, more than 56% of patients with advanced lung disease or chronic obstructive pulmonary disease are still dying in hospitals, nursing homes or long-term care facilities. Sometimes, these patients experience intrusive interventions they do not want, including intubation, CPR or mechanical ventilation. These figures highlight the importance of advance care planning in ensuring that patients’ wishes for medical care are documented and adhered to – while supporting industry efforts to provide high-quality, cost-effective care. Timely discussions about care priorities empower the patient to document their wishes in living wills and other advance directives, allowing them to receive the care they want at the appropriate time. This documentation provides clarity and prevents delays in care. Ultimately, it supports longer hospice stays and fewer hospitalizations, ICU stays and intubations. Having advance care planning conversations early on in a patient’s diagnosis is not an indication that things will get worse. Rather, it’s a responsible way to prepare patients, families and the care team if the need arises.