Add-On Clarithromycin Pans Out in Community-Acquired Pneumonia Trial


A close up photo of a clarithromycin tablet lying on its blisterpack

In a phase III trial, the addition of oral clarithromycin to beta-lactam antibiotic treatment improved the clinical response of people with community-acquired pneumonia who had systemic inflammatory response syndrome, findings that support existing guidelines.

In the study, the proportion of patients meeting the primary composite endpoint after 72 hours of treatment — fulfilling criteria for both respiratory symptom improvement and an early dampening of the inflammatory burden — reached 68% of those randomized to clarithromycin atop standard care and 38% of those receiving beta-lactam antibiotics alone (OR 3.40, 95% CI 2.06-5.63), reported Evangelos Giamarellos-Bourboulis, MD, of the National and Kapodistrian University of Athens, Greece, and coauthors.

Additionally, the combination of antibiotics significantly reduced the risk for subsequent organ dysfunction, prevented development of new sepsis, and shortened the time to hospital discharge, according to the double-blind ACCESS trial published in Lancet Respiratory Medicineopens in a new tab or window.

“Our results suggest that clarithromycin should be added to the management of hospitalized patients with community-acquired pneumonia to alleviate the inflammatory burden and to achieve early clinical benefit,” the group wrote.

Serious treatment-emergent adverse events (TEAEs) out to 90 days occurred in similar numbers between groups (43% vs 53%; OR 1.46, 95% CI 0.89-2.35).

Time-to-event curves suggested most of the benefit of the macrolide occurred in the first 8 days. The investigators added that they had indirect evidence of clarithromycin having a strong effect at the level of immune function — given that the clarithromycin group produced more tumour necrosis factor-α and less interleukin-10 in response to lipopolysaccharide stimulation than patients in the placebo group at day 4 — though cautioned that the antibiotic should still be used with caution to avoid emergence of resistance.

“Perhaps the most intriguing aspect of the study was the attempt to assess how clarithromycin modified immune response,” commented Grant Waterer, MD, PhD, of the University of Western Australia and Royal Perth Hospital.

“If impairment in early downregulation of pro-inflammatory responses is beneficial, this has fundamental implications for our understanding of the pathobiology of severe sepsis. Because most of the trend to benefit in mortality with clarithromycin was observed in the first 6-7 days, primary sepsis was probably driving mortality, not a reduction in secondary infections,” he wrote in an invited commentopens in a new tab or window.

In any case, ACCESS filled the need for a good randomized trial on combining beta-lactam antibiotics and macrolides for community-acquired pneumonia, a practice that has already been recommended by American and European guidelines alike.

ACCESS was conducted at multiple public hospitals within Greece from 2021 to 2023.

Investigators sought adults requiring hospital admission who were experiencing two or more community-acquired pneumonia-related symptoms such as cough, dyspnoea, pleuritic chest pain, or purulent sputum expectoration. Participants were ineligible if they had any history of contact with the hospital environment or with healthcare facilities during the preceding 90 days.

Patients also needed to exhibit two or more criteria for systemic inflammatory response syndrome, have a total Sequential Organ Failure Assessment (SOFA) score of at least 2, and have a procalcitonin concentration of at least 0.25 ng/mL.

A total of 278 patients were enrolled in the trial and randomized to standard care with or without oral clarithromycin (500 mg tablets every 12 hours for a week). Over 60% of the patient population were men, and all of the patients were white.

Individual components of the primary endpoint all favored the clarithromycin group over controls:

  • Decreases in respiratory symptom severity scores of at least 50% from baseline: 72% vs 48% (OR 2.83, 95% CI 1.70-4.70)
  • Decrease of 30% or more in SOFA score: 68% vs 41% (OR 3.10, 95% CI 1.88-5.11)
  • Favorable change in procalcitonin kinetics: 69% vs 54% (OR 1.86, 95% CI 1.12-3.06)

None of the TEAEs were found to be related to the study treatments. The most common events were septic shock, anemia, and SARS-CoV-2 infection, all of which were numerically more frequent among placebo patients.

As for the trial’s limitations, researchers noted that there was a heavy inflammatory burden among the patients enrolled and that the pathogen was ultimately found in 55% of the patient population, distinguishing ACCESS from other studies.

“Questions undoubtedly remain over the role of macrolides in community-acquired pneumonia,” Waterer wrote. “The threshold of severity for mandatory use is unclear and further studies are needed at lower thresholds, acknowledging that many patients with mild community-acquired pneumonia will have good outcomes regardless of the therapy chosen.”

Could Inhaling a Statin Help Ease Asthma, COPD?


News Picture: Could Inhaling a  Statin Help Ease Asthma, COPD?By Ernie Mundell HealthDay Reporter

FRIDAY, Jan. 5, 2024

Drugs already used by millions to lower cholesterol might someday have a new role: Relieving asthma and COPD.

That’s the hope of a new line of research underway at the University of California, Davis.

A study funded by the U.S. National Institutes of Health is seeking to determine whether a “statin inhaler” might reduce the airway inflammation that makes breathing difficult for folks with illnesses like asthma or chronic obstructive pulmonary disease (COPD).

Taking a statin pill has no significant effect on the airways, but “delivering statins directly to the lung via inhalation might achieve better local tissue drug levels, and therefore, better clinical results,” theorized lead investigator Amir Zeki, a professor of internal medicine who specializes in pulmonary, critical care and sleep medicine at UC Davis.

This research is still in its early stages. However, if it pans out it might offer another treatment option to the more than 26.5 million Americans with asthma and the more than 16 million battling COPD.

Zeki’s team is focusing on what’s known as airway smooth muscle (ASM) — tissue which lies within each airway’s wall and helps control airflow.

The inflammation that drives asthma can trigger a tightening of smooth muscle, restricting airways. This “hyperactivity” of smooth muscle also plays a role in COPD, the researchers explained.

Treatments such as asthma bronchodilators already target receptors on specific smooth muscle cells, triggering a healthy relaxation of the muscle. But these meds aren’t always effective.

“Despite their widespread use, current inhaler therapies that treat asthma and COPD remain inadequate in controlling symptoms for many patients, especially those with moderate to severe disease,” Zeki said in a UC Davis news release. “For this reason, we need novel inhaled medications to treat obstructive airway diseases such as asthma via mechanisms of action different from current standard-of-care therapies.”

That’s where the anti-inflammatory properties of statins come in. Studies in the lab have shown that these drugs enhance the cellular function of airways in various ways.

“To our surprise, we have discovered that statins also work as a bronchodilator, in which they directly relax ASM tissue, leading to the opening of airways,” Zeki said.

Statins taken as pills have not shown any benefit against airway disease, however. That’s because the liver breaks down drugs taken as pills, minimizing any benefit that might accrue by the time the drug makes it to an airway.

Using an inhaler to deliver a statin directly to the airway bypasses that issue.

“This allows us to deliver significantly lower doses to the airways with hopefully greater potency,” Zeki said.

Phase 1 and phase 2 clinical trials are planned in which patients with asthma and COPD will try out statin inhalers for safety and effectiveness.

“We have successfully developed a proprietary formulation that is available and ready for first-in-human testing,” Zeki said. “Our aim is to begin with asthma, but we also have plans to investigate COPD as well.”

10 Ways to Feel Better Now


photo of bowl of hot soup

You wake up with a sore throat. Then come the coughing, sneezing, and sniffling. There’s no denying it — you’re sick. Sadly, there’s no quick cure for the common cold or the flu. But you can find relief faster with these smart moves. 

Take it easy. When you’re sick, your body works hard to fight off that infection. It needs more energy than usual. Make rest your top priority. Stay home from work or school, and put your daily routine on hold until you feel better.

Go to bed. Curling up on the couch helps, but don’t stay up late watching TV. Skimping on sleep makes your immune system weak, making it harder to fight germs. Head to bed early, and take naps during the day. Are your symptoms keeping you up at night? Try using an extra pillow to raise your head. It can ease sinus pressure and help you breathe easier.  

Drink up. Getting plenty of fluids thins your mucus and breaks up congestion. It also prevents the headaches and fatigue that dehydration causes. Keep a glass or reusable bottle on hand, and refill it with water. Skip caffeinated sodas, coffee, and alcohol, which can dry you out.

Gargle with salt water. It’s a good way to soothe a throbbing throat. The salt water eases swelling and loosens mucus. Stir one-quarter to one-half teaspoon of salt into a cup of warm water until it’s dissolved, and gargle a few times a day.

Sip a hot beverage. It’s comforting to curl up with a mug of tea. Plus, research shows that the heat can also ease cold symptoms such as sore throat and fatigue. Try sipping non-caffeinated herbal tea, lemon water, or warm broth.

Have a spoonful of honey. This sticky stuff can coat your throat and soothe a cough. In one study, kids who ate about half a tablespoon of honey at bedtime slept more soundly and coughed less than those who got a placebo medicine. Stir it into a cup of decaf tea or lemon water. One warning: Don’t give honey to babies younger than 1 year old.

Take a hot shower. Breathing in steam may moisten a scratchy throat and nose, as well as loosen your congestion. Although the research is mixed on whether this remedy works, there’s no harm in trying it. The heat can also help relax any aching muscles.

Take an over-the-counter remedy. You may find relief with one of these medications. Take them as directed, and don’t give them to children under age 6 without your pediatrician’s OK.

  • Pain reliever for fever and aches. Doctors usually recommend acetaminophen. If you’re taking another cold medicine, though, check that it doesn’t already have the drug. It’s a common ingredient in many OTC remedies, but getting too much can be dangerous. So check the label and ask the pharmacist how much is safe to take at one time.
  • Lozenges for a sore throat. They have herbs and other ingredients that can soothe the stinging.
  • Decongestant for stuffiness. This medicine shrinks blood vessels in your nose so your airways can open up. But the liquid or pill form may make you feel jittery. Using decongestant sprays and drops too much can cause more congestion, so don’t use them for more than 3 days.
  • Expectorant to thin mucus. It can help loosen some of that thick discharge.
  • Antihistamine to dry up a runny nose. This drug blocks the chemical in your body that causes sneezes and sniffling.

Taking a decongestant and an antihistamine together may be more helpful than taking either one alone.

Use a saline spray or flush. Over-the-counter saltwater sprays make your nostrils moist, which makes it easier to blow your nose. You may also want to try nasal irrigation. That’s when you gently pour a saline solution into one nostril and let it flow out of the other. It washes away dried mucus so you can breathe easier. You can buy sinus rinses or use a bulb syringe or neti pot. If you do it yourself, always make the saltwater solution with distilled or cooled, boiled water.

Eat chicken soup. Mom was right: This sick-day staple really can make you feel better.  Research shows that chicken soup can calm inflammation in your body. This may ease some of your symptoms, such as aches and stuffiness. What’s more, this meal also has liquid and calories to give your body energy.

Honey Plus Coffee Beats Steroid For Treating Cough


Bee's sweet contribution to humans has been found in art throughout the ages (Julian Rovagnati/Shutterstock)

Bee’s sweet contribution to humans has been found in art throughout the ages

One of modern medicine’s most celebrated ‘miracle drugs’ are steroids, but a double-blind, randomized clinical trial found that honey plus coffee outperformed prednisolone in treating symptoms of post-infectious, persistent cough. 

A remarkable study looking at natural alternatives to medications found that compared to a systemic steroid, a combination of honey and coffee was superior in reducing symptoms associated with a post-infectious cough (PPC).

PPC is a cough that remains after a common cold or an upper respiratory tract infection for more than three weeks, and in some cases as long as several months. Conventional treatment may involve any number of powerful drugs, many of which have serious side effects, including codeine and dextromethorphan (so-called centrally acting antitussives), antihistamines, narcotics, and bronchodilators.

The study, published in Primary Care Respiratory Journalwas conducted by researchers at Baqiyatallah University Hospital, Tehran, Iran from 2008 to 2011. 97 patients who had experienced PPC for more than three weeks were randomized in double-blinded fashion into three groups:

  1. A jam like paste was prepared which consisted of 20.8 grams of honey plus 2.9 grams of instant coffee for the first group (‘HC’).
  2. 13.3 mg of prednisolone for the second group (steroid, ‘S’).
  3. 25 mg of guaifenesin for the third group (control, ‘C’).

The researchers described the patient treatment protocol as follows:

“The participants were told to dissolve a specified amount of their product in warm water and to drink the solution every eight hours for one week. All the participants were evaluated before treatment and one week after completion of treatment to measure the severity of their cough. The main outcome measure was the mean cough frequency before and after one week’s treatment calculated by a validated visual analogue cough questionnaire score.”

The results of the study are summarized in the following table:

Coffee Honey Beats Prednisone

As you can see by the table above, the honey-coffee group saw their degree of cough frequency decrease from 2.9 before treatment to .2 after treatment, whereas the prednisolone group decreased only from 3.0 before treatment to 2.4 after treatment.

They detailed are as follows:

“RESULTS: There were 97 adult patients (55 men) enrolled in this study with the mean of age of 40.1 years. The mean (+/- SD) cough scores pre- and post-treatment were: HC group 2.9 (0.3) pre-treatment and 0.2 (0.5) post-treatment (p < 0.001); steroid (‘S’) group 3.0 (0.0) pre-treatment and 2.4 (0.6) post-treatment (p < 0.05); control (‘C’) group 2.8 (0.4) pre-treatment and 2.7 (0.5) post-treatment (p > 0.05). Analysis of variance showed a significant difference between the mean cough frequency before and after treatment in the HC group versus the S group (p< 0.001). Honey plus coffee was found to be the most effective treatment modality for PPC. “[emphasis added]

The researchers reflected on the implications of their findings:

“Each year, billions of dollars are spent on controlling and trying to cure cough while the real effect of cough medicines is not quite reliable.1,45 Even though PPC is reported to account for only 11–25% of all cases of chronic cough8 and it is not associated with disability and mortality, it can cause morbidity and is responsible for medical costs…13

Honey and coffee are natural edible substances that are safe, agreeable, less expensive than medicines, and easily available. Moreover, they have proved to be effective in a short period of time.”

Prednisone is a semi-synthetic hormone with a broad range of side effects, some of which are life threatening. Given the relative safety and superior effectiveness of honey plus coffee versus prednisolone, this study adds to a growing body of biomedical research indicating that natural substances, including spices, vitamins and foods, are often superior in efficacy to synthetic drugs while often maintaining far higher levels of safety relative to them.

What is the comparison between the use of antitussives and mucolytics in the management of cough?


AntitussivesMucolytics
Antitussive drugs act in the central nervous system (CNS) and increase the threshold of the cough centre or act peripherally in the respiratory tract to decrease tussal impulses or both these actions.Mucolytic drugs act on the mucous layer of the respiratory tract to enhance its clearance. These medications break down the polymer bonds within the secretions.
Antitussives are recommended for:dry non-productive cough unduly tiring coughsleep disturbing coughhazardous cough (piles, hernia, cardiac disease, ocular surgery).Mucolytics are recommended to manage mucus hypersecretion and its sequelae like recurrent infection in patients suffering from:cystic fibrosischronic obstructive pulmonary disease (COPD)bronchiectasis.
As per the Clinical Practice Guidelines for Diagnosis and Management of Cough by the Chinese Thoracic Society (CTS) Asthma Consortium- central or peripheral acting antitussive agents are recommended for patients with severe dry cough.As per the Clinical Practice Guidelines for Diagnosis and Management of Cough by the Chinese Thoracic Society (CTS) Asthma Consortium- mucolytics can improve cough in patients with difficulty expectorating sputum. 
As per the Belgian Guidelines, antitussives are contra-indicated in paediatric patients (age < 6 years). Their use is also not recommended in patients between 6 to 12 years.As per the Belgian Guidelines, mucolytics are contra-indicated in patients (age < 2 years). Guaifenesin is contra-indicated in children below 6 years. Mucolytics are also not recommended in children between 6 to 12 years.
According to the Indian guideline, central antitussives are recommended in early onset of whooping cough, haemoptysis and post-surgery, and dry cough with sleep disturbance and pain. Dextromethorphan is the preferred central antitussive drug.[1] Peripheral antitussive – Levodropropizine is recommended in non-productive cough.[1]According to the Indian guideline, mucolytics can be used to facilitate mucus clearance in children with chronic cough.
Codeine is an opioid (antitussive drug) used for the symptomatic treatment of acute cough in children (aged >12 years). However, clinical studies do not substantiate the effectiveness of this drug in the management of acute cough. Moreover, the side effects of Codeine restrict the use of this drug for cold and cough in children younger than 18 years of age.A study in India reported that Dextromethorphan and Codeine are mostly recommended for the management of cough in paediatric patients. The commonly prescribed mucolytics include Bromhexine, Ambroxol, Acetyl cysteine, Carbocysteine.Erdosteine, a mucolytic drug, is used for the treatment of chronic obstructive pulmonary disease. A clinical study tried to determine the effect of Erdosteine used in combination with an antibiotic (Amoxicillin) for the treatment of cough in children. Significant cough reduction was documented in the group treated with Erdosteine and Amoxicillin.Letosteine used at a dose of 25 mg 3 times daily for 10 days in children (age 2 to 12 years) with acute febrile bronchitis was also effective in alleviating acute cough.  Clinical studies claimed that Guaifenesin, another mucolytic drug, was effective in the management of symptoms in children (age 12 years and above) suffering from upper respiratory tract infection.[2]

Citation

  1. ab Paramesh H, Mohanty NC, Kumar R, Kumar P, Sivabalan S, et al. Airway Disease Education & Expertise (ADEX) NEXT working group recommendations-persistent (Chronic) cough in pediatric practice. Journal of the Pediatrics Association of India. 2017 Oct 1;6(4):230.https://nijp.org/wp-content/uploads/2018/01/v6n4-p230-243.pdf
  2. ^ Marseglia GL, Manti S, Chiappini E, et al. Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology. Allergol Immunopathol (Madr). 2021;49(2):155-169. doi:10.15586/aei.v49i2.45 https://www.all-imm.com/index.php/aei/article/view/45/229#figures

Honey Plus Coffee Beats Steroid For Treating Cough


One of modern medicine’s most celebrated ‘miracle drugs’ are steroids, but a recent double-blind, randomized clinical trial found that honey plus coffee outperformed prednisolone in treating symptoms of post-infectious, persistent cough. 

Honey Plus Coffee Beats Steroid For Treating Cough

A remarkable new study looking at natural alternatives to medications found that compared to a systemic steroid, a combination of honey and coffee was superior in reducing symptoms associated with a post-infectious cough (PPC).

PPC is a cough that remains after a common cold or an upper respiratory tract infection for more than three weeks, and in some cases as long as several months. Conventional treatment may involve any number of powerful drugs, many of which have serious side effects, including codeine and dextromethorphan (so-called centrally acting antitussives), antihistamines, narcotics, and bronchodilators.

The new study, published in Primary Care Respiratory Journal, was conducted by researchers at Baqiyatallah University Hospital, Tehran, Iran from 2008 to 2011.[i] 97 patients who had experienced PPC for more than three weeks were randomized in double-blinded fashion into three groups:

  1. A jam like paste was prepared which consisted of 20.8 grams of honey plus 2.9 grams of instant coffee for the first group (‘HC’).
  2. 13.3 mg of prednisolone for the second group (steroid, ‘S’).
  3. 25 mg of guaifenesin for the third group (control, ‘C’).

The researchers described the patient treatment protocol as follows:

“The participants were told to dissolve a specified amount of their product in warm water and to drink the solution every eight hours for one week. All the participants were evaluated before treatment and one week after completion of treatment to measure the severity of their cough. The main outcome measure was the mean cough frequency before and after one week’s treatment calculated by a validated visual analogue cough questionnaire score.”

The results of the study are summarized in the following table:

Coffee Honey Beats Prednisone

As you can see by the table above, the honey-coffee group saw their degree of cough frequency decrease from 2.9 before treatment to .2 after treatment, whereas the prednisolone group decreased only from 3.0 before treatment to 2.4 after treatment.

They detailed are as follows:

RESULTS: There were 97 adult patients (55 men) enrolled in this study with the mean of age of 40.1 years. The mean (+/- SD) cough scores pre- and post-treatment were: HC group 2.9 (0.3) pre-treatment and 0.2 (0.5) post-treatment (p < 0.001); steroid (‘S’) group 3.0 (0.0) pre-treatment and 2.4 (0.6) post-treatment (p < 0.05); control (‘C’) group 2.8 (0.4) pre-treatment and 2.7 (0.5) post-treatment (p > 0.05). Analysis of variance showed a significant difference between the mean cough frequency before and after treatment in the HC group versus the S group (p< 0.001). Honey plus coffee was found to be the most effective treatment modality for PPC. [emphasis added]

The researchers reflected on the implications of their findings:

“Each year, billions of dollars are spent on controlling and trying to cure cough while the real effect of cough medicines is not quite reliable.1,45 Even though PPC is reported to account for only 11–25% of all cases of chronic cough8 and it is not associated with disability and mortality, it can cause morbidity and is responsible for medical costs…13

Honey and coffee are natural edible substances that are safe, agreeable, less expensive than medicines, and easily available. Moreover, they have proved to be effective in a short period of time.”

Given the relative safety and superior effectiveness of honey plus coffee versus prednisolone, this study adds to a growing body of biomedical research indicating that natural substances, including spices, vitamins and foods, are often superior in efficacy to synthetic drugs while often maintaining far higher levels of safety relative to them.

Vaccination Opt-Outs Found to Contribute to Whooping Cough Outbreaks in Kids.


Several factors may be contributing to recent whooping cough outbreaks, but parents’ refusal to immunize their children is one

A California whooping cough epidemic in 2010 was one of the worst U.S. outbreaks of the disease in the past several decades. Ten infant deaths occurred among the more than 9,000 cases—the most in that state since 1947. Now, a study reveals that parental refusals to vaccinate their children may have played a part in that epidemic and possibly in a concurrent nationwide resurgence of the disease. The research found significant overlaps of areas with high numbers of whooping cough cases and areas where more parents had sought legal exemptions to opt out vaccinating their children.

 

CAUSE FOR WHOOPING COUGH‘S RESURGENCE?: Research shows California’s rates of nonmedical vaccine exemptions tripled from 0.77 percent in 2000 to 2.33 percent in 2010, and some schools had 2010 nonmedical exemption rates as high as 84 percent.

 

Whooping cough, or pertussis, is a highly contagious bacterial infection in the lungs that causes violent coughing and sometimes lasts for months. A combination vaccine called the DTaP (for diphtheria,tetanus, and acellular pertussis) protects children up to six years old from pertussis, and a similar formulation called Tdap is used to protect older children and adults.Previous research has found, however, that neither vaccine, made from the pertussis toxin and other genetic pieces of the bacterium, is as effective as DTP vaccine, a preparation that contained the whole bacterial cell; it was discontinued in the 1990s. Accordingly, pertussis cases remained low when DTP was the standard of care—typically fewer than 5,000 U.S. cases annually—but made a comeback in the past decade.

Parents in many states may opt out of vaccinating their children by seeking legal exemptions to public school immunization requirements. All but two states—Mississippi and West Virginia—allow religious exemptions, and 19 states, including California, offer some variation of a philosophical or “personal belief” exemption, depending on the law’s language. California’s rates of nonmedical exemptions tripled from 0.77 percent in 2000 to 2.33 percent in 2010, and some schools had 2010 nonmedical exemption rates as high as 84 percent.

In the new study, published September 30 in Pediatrics, lead author Jessica Atwell and her colleagues mapped “clusters”—statistically unusual aggregations—of nonmedical exemptions for kindergartners between 2005 and 2010. Theresearchers identified 39 clusters of such opt outs, including one that covered nearly all of northern California. In each of these clusters the area covered contained a statistically higher concentration of kindergartners with exemptions than the areas outside the clusters. Atwell’s team then used a similar modeling method to identify two pertussis outbreak clusters—areas where the cases reached statistically higher numbers than the rest of California. One such cluster included most of central California between May and October 2010. The other included San Diego County between July and November 2010. Then the researchers analyzed the clusters’ overlap.

“The strength of our approach was not just to find out the clustering of cases but also the statistical significance of the clustering overlap,” says senior author Saad Omer, an associate professor at Emory University School of Medicine’s Vaccine Center. “This tells us whether the clustering is by chance or not.” Neither the clusters nor their overlapping was by chance. Census tracts within a nonmedical exemption cluster were 2.5 times more likely to be within a pertussis cluster, even after accounting for population characteristics including racial demographics, population density, household income, average family size, percentage of residents with a college degree and location within a metropolitan area. Residents living in a census tract within a nonmedical exemption cluster were 20 percent more likely to catch pertussis than those outside a cluster, the analysis revealed.

Past research has already revealed that the weaker vaccine is driving whooping cough outbreaks and epidemics in the past decade. The new findings reveal there is more to the story. “What this study tells us is that if more and more people choose not to get a vaccine,” says Paul Offit, director of the Vaccine Education Center at The Children’s Hospital of Philadelphia, “then you’ll have bigger and bigger outbreaks.” This study also backs up the results in a 2008 study led by Omer that similarly found overlaps in pertussis outbreaks and nonmedical exemptions in Michigan during an 11-year period.

Atwell, a PhD candidate in Global Disease Epidemiology and Control at the Johns Hopkins Bloomberg School of Public Health, says it is difficult to quantify the contributions of different factors to the resurgence of pertussis and that it is a multifaceted issue. “There are a lot of factors, including waning immunity from the vaccine, increased case detection and possible changes in circulating strains,” she says, “but our study shows that nonmedical exemptions and clustering of unvaccinated individuals may have also played a role.”

Public health efforts to prevent epidemics of infectious diseases typically rely onherd immunity: The more people in a community are vaccinated or otherwise protected from a disease, the less likely it is to be transmitted throughout the population. This approach is particularly crucial with pertussis, which is almost as contagious as measles and requires about 95 percent vaccination coverage to maintain herd immunity. Increasing numbers of parents opting out of vaccinating their children can erode this immunity. “When you look at statewide or countywide data, the increases in nonmedical exemptions don’t look that significant,” Atwell says, “but when you look at community-wide coverage, it is much lower than the threshold needed to maintain herd immunity in some areas.”

Unvaccinated individuals in the 2010 epidemic were eight times more likely to contract pertussis than vaccinated ones. But unvaccinated individuals pose risks to the community as well. “It’s a choice you make for yourself and a choice you make for those around you,” Offit says. “Infants need those around them to be protected in order not to get sick. We have a moral and ethical responsibility to our neighbors as well as to ourselves and our children.”

Data has shown exemptions are more prevalent where they are easier to obtain. In California parents currently can obtain exemptions simply by signing a form. A law takes effect there next year requiring parents to meet with a health care provider before obtaining an exemption. “I hope the legislation will help address the increased risk for pertussis and raise immunization rates in those areas,” says Richard Pan, a pediatrician and member of the California State Assembly who sponsored the bill. He says the law may not effect much change in areas with strong pockets of vaccine-refusing parents, but he hopes more of the parents feeling uncertain about immunization will realize the benefits after getting accurate information from a health care professional.

Parents who turn down vaccinations for their children are often misinformed aboutthe safety and effectiveness of vaccines. “I don’t think people understand that our control of vaccine-preventable diseases such as pertussis and measles is fragile,” Atwell says. “We need to continue to educate people about the implications of not vaccinating their children.”

 

 

 

 

 

Antireflux Surgery in Patients With Chronic Cough and Abnormal Proximal Exposure as Measured by Hypopharyngeal Multichannel Intraluminal Impedance.


Importance  Chronic cough is a laryngeal symptom that can be caused by gastroesophageal reflux disease; however, treatment outcome has been difficult to predict because of the lack of an objective testing modality that accurately detects reflux-related cough.

Objective  To define the patterns of reflux and assess the outcome of antireflux surgery (ARS) in patients with chronic cough who were selected using hypopharyngeal multichannel intraluminal impedance (HMII).

Design  Review of prospectively collected data.

Setting  Tertiary care university hospital.

Participants  Patients with chronic cough, which was defined as persistent cough (≥8 weeks) of unknown cause.

Interventions  Hypopharyngeal multichannel intraluminal impedance with a specialized catheter to detect laryngopharyngeal reflux and high-esophageal reflux (reflux 2 cm distal to the upper esophageal sphincter) and ARS.

Main Outcomes and Measures  Abnormal proximal exposure was defined as laryngopharyngeal reflux occurring 1 or more times per day and/or high-esophageal reflux occurring 5 or more times per day. The outcomes of ARS included symptomatic improvement.

Results  From October 2009 to June 2011, a total of 314 symptomatic patients underwent HMII. Of this population, 49 patients (15 men, 34 women; median age, 57 years) were identified as having chronic cough. Of the 49 participants, 23 of 44 patients (52%) had objective findings of gastroesophageal reflux disease, such as esophagitis. Abnormal proximal exposure was discovered in 36 of the 49 patients (73%). Of 16 patients with abnormal proximal exposure who subsequently underwent ARS, 13 patients (81%) had resolution of cough and 3 patients (19%) had significant improvement at a median follow-up of 4.6 months (range, 0.5-13 months).

Conclusions and Relevance  A highly selective group of patients with idiopathic chronic cough may have abnormal proximal exposure to gastroesophageal reflux documented by HMII that would have not been detected with conventional pH testing. Thus, HMII is likely to improve the sensitivity of laryngopharyngeal reflux diagnosis and better elucidate those who will respond to antireflux surgery.

 

Source: JAMA

 

 

 

Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease..


Epidemiologic and physiologic studies suggest an association between gastroesophageal reflux disease (GERD) and chronic cough. However, the benefit of antireflux therapy for chronic cough remains unclear, with most relevant trials reporting negative findings. This systematic review aimed to reevaluate the response of chronic cough to antireflux therapy in trials that allowed us to distinguish patients with or without objective evidence of GERD.

METHODS: PubMed and Embase systematic searches identified clinical trials reporting cough response to antireflux therapy. Datasets were derived from trials that used pH-metry to characterize patients with chronic cough.
RESULTS: Nine randomized controlled trials of varied design that treated patients with acid suppression were identified (eight used proton pump inhibitors [PPIs], one used ranitidine). Datasets from two crossover studies showed that PPIs significantly improved cough relative to placebo, albeit only in the arm receiving placebo fi rst. Therapeutic gain in seven datasets was greater in patients with pathologic esophageal acid exposure (range, 12.5%-35.8%) than in those without (range, 0.0%-8.6%), with no overlap between groups.
CONCLUSIONS: A therapeutic benefit for acid-suppressive therapy in patients with chronic cough cannot be dismissed. However, evidence suggests that rigorous patient selection is necessary to identify patient populations likely to be responsive, using physiologically timed cough events during reflux testing, minimal patient exclusion because of presumptive alternative diagnoses, and appropriate power to detect a modest therapeutic gain. Only then can we hope to resolve this vexing clinical management problem.

Source: Chest

 

Measuring Aerosol Production from Patients with Active TB.


Twenty-eight of 101 patients with culture-confirmed pulmonary tuberculosis had culture-positive cough aerosols, suggesting infectiousness; likelihood of a culture-positive aerosol was directly correlated with degree of sputum-smear positivity.

Although tuberculosis (TB) is transmitted by aerosols of droplet nuclei <5 µm in diameter, determination of infectiousness has been based on microscopic examination of sputum for the presence of organisms (smear assessment) — a method that may be neither sensitive nor specific. The magnitude and particle-size distributions of the aerosols generated by patients with active TB are unknown.

In a study conducted in Uganda, researchers attempted to collect, quantify, and size the aerosols produced by voluntary coughing in patients with active pulmonary TB and to compare these findings with results from sputum smears and aerosol cultures. Patients with culture-confirmed TB were asked to cough in two 5-minute sessions into a custom-built chamber that analyzed and collected their cough aerosol. Plates within the chamber contained 7H11 agar for mycobacterial culture.

Among the 101 patients, 28 produced aerosols that grew Mycobacterium tuberculosis. The proportion of patients who generated culture-positive aerosols increased significantly as the sputum smear microscopy grade increased (P=0.03). All patients with a culture-positive aerosol were smear positive; none of those with a negative smear produced a culture-positive aerosol. More than 96% of the culturable particles collected were between 0.7 and 4.7 µm in diameter.

Comment: Although the authors conclude that cough aerosols might provide a better determination of infectiousness than smear assessment, the data indicate that smear results correlate well with aerosol culture results.

Source: Journal Watch Infectious Diseases