Non–Cystic Fibrosis (CF) Bronchiectasis in Adults
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From the JAMA Network, this is JAMA Clinical Reviews, interviews and ideas about innovations in medicine, science, and clinical practice. Hello, and welcome to our listeners around the world. I'm Dr. Kristen Walter, Deputy Editor at JAMA. I'm joined today by Dr. Alan Barker, who is Professor of Medicine in the Department of Pulmonary Allergy and Critical Care at Oregon Health and Science University.

Today, we will be discussing a study that he co-authored with Dr. Eli Karamoos titled Non-Cystic Fibrosis, Bronchiectasis in Adults, a Review. This article was published online in JAMA on April 28th. Thank you for joining this podcast. Thank you. Look forward to it.

Before starting, I'd like to point out that your article does not discuss cystic fibrosis, which is a genetic condition that causes bronchiectasis and was covered in a JAMA review article in June 2023. Therefore, throughout this podcast, when we use the term bronchiectasis, we will be referring to non-cystic fibrosis bronchiectasis. To start out, can you talk about the definition of bronchiectasis?

Sure. Bronchiectasis involves a clinical paradigm plus chest CT imaging. The clinical paradigm is a chronic cough accompanied by mucopurulent sputum on most days of the week, often interrupted by exacerbations. The chest CT has become the defining objective tool to confirm bronchiectasis.

The findings on chest CT, and it does not have to be accompanied by contrast, are dilated airways greater than the diameter of an accompanying blood vessel. There is often thickening of the airways representing inflammation.

The airways may be accompanied with tenacious mucus seen in bronchi as far out as bronchioles, and the dilated airways do not taper as normal airways to the periphery. They are often tortuous, and one may see on the periphery of the lung the mucus-filled small bronchioles filled with mucus, so-called tree and bud.

And can you discuss the pathophysiology of bronchiectasis? Bronchiectasis includes several pathophysiologic phenomena. One, there is infection. Non-tuberculous mycobacterium, such as mycobacterium avium intracellulari, hemophilus, and sometimes other bacteria, such as Staphylococcus aureus.

Occasional fungi may also be involved in that infection, particularly Aspergillus fumigatus. Secondly, there is inflammation, and the predominant inflammatory cell is the neutrophil. There is excessive neutrophil permeation throughout the airway, and this is accompanied by enzymatic release of a variety of enzymes, most notably elastase.

The final feature accompanying bronchiectasis is the accumulation of mucus. So you mentioned cough and sputum as the most common symptoms of patients with bronchiectasis, but can you discuss some other symptoms that people might experience? Let me just emphasize on the sputum production. This is often different than patients with chronic bronchitis or part of COPD.

The mucus is thick. It's often off-color, yellowish-brown, in contradistinction to many individuals with chronic bronchitis, in which it's sort of mucoid, light gray, or even white. Other symptoms include malaise or fatigue. Occasionally, they will present with low-grade fevers, and then most distressing,

and can lead to major morbidity, of course, is coughing up blood. Because of the combination of infection and inflammation in the submucosal area, there is neovascularization, and the overlying mucosa can break down, and these individuals can either cough up bloodstream sputum, or if it's an arterial, maybe major bleeding that requires immediate medical attention.

Can you discuss the epidemiology of bronchiectasis? How many people in the U.S. have this condition, and is it more common in women or men? The average age of bronchiectasis is in the mid-60s or even older up into the late 60s.

There is estimated from Medicare evaluation of large databases about 350,000 individuals in the United States affected with bronchiectasis. Larger insurance-based studies suggest there's probably another 175,000 individuals affected with bronchiectasis.

making somewhere around 500,000 plus individuals with bronchiectasis in the United States. This, of course, is a worldwide disease, and there are quite a number of variabilities on bronchiectasis populations, as one might imagine in other countries. The disease affects women more than men. In some studies, as much as twice as many women are seen as men.

Bronchiectasis is caused by or associated with a variety of different medical conditions. I was hoping you could describe some of the most common conditions associated with non-cystic fibrosis bronchiectasis.

Even though in most large registries or population studies, anywhere up to 40% of individuals with bronchiectasis, as confirmed by the CT, have no etiology or idiopathic, there are several underlying conditions that we should think about as we are evaluating and treating our patient with bronchiectasis. Certainly, infection is important.

I mentioned non-tuberculous mycobacteria. Cultures that grow out pseudomonas are an important signal of underlying bronchiectasis. Underlying genetic conditions we occasionally see, those include alpha-1 antitrypsin deficiency,

Other conditions include underlying rheumatic diseases or collagen vascular diseases, particularly rheumatoid arthritis, Sjogren's disease, and inflammatory bowel disease. Not to be missed, which can be either congenital or appear later in life, is immunodeficiency, particularly B-cell derived, such as hypogammaglobulinemia.

And then associated conditions should also be sought, examined for during history taking and perhaps laboratory studies. They include asthma, chronic obstructive pulmonary disease, and esophageal reflux disease. After a patient is diagnosed with bronchiectasis, which initial blood tests and sputum testing should clinicians order?

After confirmation of the diagnosis with a chest CT, the following are important basic tests. A complete blood count with a differential is key. The presence of eosinophils, percentage greater than 2 to 3 percent, should at least raise a suspicion of underlying atopy or even asthma.

or bronchopulmonary aspergillosis, or ABPA, allergic bronchopulmonary aspergillosis. Even though immunodeficiency is relatively uncommon, it is treatable by replacement therapies of IgE. So an immunoglobulin panel of IgG, A, M, and E should be obtained as basic initial laboratory studies.

Sputum cultures. These individuals have chronic sputum production, and an AM sputum is usually not hard to raise, and a sterile sputum container can be provided to the patient and can be brought back into the laboratory to be analyzed for bacteria, which would include mycobacteria, as well as fungi.

In those individuals, and there are some with bronchiectasis that either have scant sputum or unable to raise the sputum, we may need to bring them in to the hospital or the laboratory and induce a sputum with nebulized saline. Or we may need to do bronchoscopy with bronchoalveolar lavage. That would be uncommon. Most of these patients can raise plenty of sputum

And general sputum cultures are key. Patients with bronchiectasis also should have spirometry. Are there characteristic findings on spirometry in patients with bronchiectasis? Spirometry indeed is part of the initial evaluation to provide a functional assessment and also to guide therapy.

Initial testing should include spirometry, usually with a bronchodilator. Albuterol is the classic one used in most laboratories. About 50% to 75% of individuals with bronchiectasis will have an obstructive pattern on spirometry. That includes a reduced forced expiratory volume in one second,

divided by the forced vital capacity, or FVC, less than the lower limit of normal, usually around 70%. About a quarter of those patients will have an improvement in the FEV1 and or the FVC after the administration of albuterol that will help guide whether a patient may benefit from a bronchodilator. Lung volumes and diffusion

are additional tests, but the spirometry with bronchodilator is prime. You mentioned exacerbations of bronchiectasis earlier, and they are one of the most important complications of this condition. Can you define an exacerbation for us? Exacerbations include several of the following.

the cough increases. The sputum changes color. If it was pale yellow, some patients have it as clear. It becomes darker in color towards yellow or brown, sometimes admixed with streaks of blood or even more blood. So the presence of increased blood streak sputum hemoptysis is another signal.

malaise or fatigue that I discussed earlier increases. Fever is uncommon during an exacerbation, but certainly may occur if they have an accompanying pneumonia. And the final criteria for definition is that these symptoms should be present for somewhere on the order of 36 to 48 hours and

and attention should be sought with their medical provider as quickly as possible. And what are the clinical consequences of an exacerbation of bronchiectasis? The most common problem in patients with bronchiectasis is that each exacerbation is a huge risk factor for the next exacerbation. So the morbidity with an exacerbation is not just feeling terrible,

It is the possibility of need to be seen in emergency and even hospitalization because parenteral antibiotics are provided. The downsides after an exacerbation have been well described. They include a decline in pulmonary function, a decline in the quality of life. And this has been assessed by questionnaire data and even an increased mortality rate

if exacerbations continue and occur as often as two to three times a year. Can you describe airway clearance techniques and devices that can be used by patients with bronchiectasis? Yes. ACT or airway clearance therapy or techniques involves several modalities.

Certainly exercise or guided exercise by professionals, so-called pulmonary rehabilitation, may not be thought of as part of airway clearance, but exercise will help people expand their chest and even enhance the ability to expectorate or to remove this tenacious phlegm. So regular exercise is probably one of the first modalities.

The second would be the use of some form of device to help keep open the airways. This could be done by special coughing techniques that can be taught to patients, or there certainly are webinars. A common one used in the United States is the so-called huff or huffy technique in which the patient is counseled to take a slow, deep breath.

hold their breath, and then exhale slowly. And as they do that, they make a huffy kind of noise. That can also be combined with any number of technical modalities that are available both online and by prescriptions, such as positive expiratory pressure devices. They're not very expensive.

The positive expiratory pressure devices, or PEP valves, can have a flutter attachment that provides a little vibration to help loosen secretions. These would be used by the patient several times a day, both when they are in their stable state and also when they're having an exacerbation.

In the United States, the use of oscillatory devices in which a vibratory vest is attached to the chest and is either controlled by battery or electricity to provide that external vibration to the chest to help loosen secretions.

Not as popular in this country, but certainly outside the United States, is the use of what I would call traditional chest physical therapy, in which the patient is positioned, often with the head down, side to side.

often accompanied by a respiratory therapist or in Europe and Great Britain by a physiotherapist that performs either hand or mechanical vibratory manipulation to the chest, either at the same time or in conjunction with the positioning. That's what's traditionally called chest physical therapy.

Because of the time commitment and sometimes the difficulty of chest physical therapy, the oscillatory devices and the PEP valves in the United States have probably replaced the chest physical therapy. The third modality that's part of airway clearance is nebulization of solutions that may help break up

the DNA, and other debris that causes the tenacious phlegm. The most popular and probably the best modalities these days are some form of saline, either hypertonic saline, either 6%, 7%, or even normal saline. A nebulizer is required, although many of these patients have a nebulizer for administration of bronchodilators.

And the saline can be administered two to three times a day, depending on the tenacity and thickness of the phlegm. And when should patients with bronchiectasis use short-acting or long-acting inhalers? Bronchodilators, which would include short-acting albuterol and longer-acting bronchodilators, which could be either a beta agonist or an anti-muscarinic agent,

are most useful when there is accompanying asthma or chronic obstructive pulmonary disease. And that's why pulmonary function is important to help identify those individuals that respond. And can you discuss the role of inhaled antibiotics in patients with bronchiectasis?

One of the goals of therapy is to reduce those exacerbations. Defined variably as having two or more exacerbations in a year. And that's where the role of inhaled antibiotics comes into use.

In the United States, and actually Europe and Great Britain, there are no approved inhaled antibiotics. But at least seven have been tested through phase two and even phase three studies. And there are two or three that have shown promise and have been used off-label. They include gentamicin.

And this would be the gentamicin that is approved for intravenous use. It's been available a long time. And specialty pharmacies can make up solutions to be used. The other one that has recently been reported with efficacy is colistin, which also can be delivered using the intravenous product.

The other agent that has some utility and is available in the United States but not approved for bronchiectasis is tobramycin. A nebulizer is required for each of these agents. And for the first two, a specialty pharmacy needs to be included because they need to be made under a special hood in a sterilized atmosphere.

And moving on to recommended treatments for acute exacerbations, can you describe what is typically recommended and what about patients with severe exacerbations? Part of the initial workup and even following patients is a bacterial sputum culture to identify what is the so-called resident bacterial flora.

in the airways. This will be helpful as an exacerbation may occur. The usual cause of an exacerbation

is probably acute bacterial infection, although viruses may occasionally cause an acute exacerbation, particularly during times of endemic SARS-CoV-2 or during the influenza season. If the resident flora is Haemophilus influenzae, which is a commonly cultured organism in bronchiectasis,

prompt treatment with an antibacterial agent, which would first line include amoxicillin or amoxicillin clavulonate if type B hemophilus is cultured, or doxycycline. If that sputum culture that is known has grown pseudomonas aeruginosa, probably neither of those agents would be effective. And for oral therapy, one would have to use quinolone, and the preferred agent is ciprofloxacin.

either 750 milligrams twice a day or in a smaller individual, 500 milligrams twice daily. You may have noticed that I did not mention azithromycin, which is probably the number one agent used in so-called acute bronchitis in a relatively healthy individual or even individuals with asthma or COPD when there is suspect bacterial infection.

I generally avoid azithromycin in the bronchiectasis population because these individuals, as mentioned earlier, may have non-tuberculous mycobacteria.

one of the mainstays of treatment is the use of azithromycin. And if we use azithromycin for acute bronchitis, resistance may develop and the agent will not be useful or as helpful if there is non-tuberculous mycobacterial infection. If an individual comes in with hypotension, tachycardia, high-grade fever,

or otherwise debilitated, hospitalization is certainly warranted. And each of those individuals will require potentially supplemental oxygen and almost always broad-spectrum intravenous antibiotic medications. And those would probably include an agent effective against Pseudomonas aeruginosa,

and consideration of treatment against Staphylococcus aureus until a culture is available, vancomycin or venazolid.

Thank you so much for sharing your thoughts about this interesting and important topic. I'm Dr. Kristen Walter, and I've been speaking with Dr. Alan Barker from Oregon Health and Science University. You can find a link to the article in this episode's description. To follow this and other JAMA Network podcasts, please visit us online at jamanetworkaudio.com or search for JAMA Network wherever you get your podcasts.

This episode was produced by Daniel Morrow at the JAMA Network. Thanks for listening. This content is protected by copyright by the American Medical Association with all rights reserved, including those for text and data mining, AI training, and similar technologies.