Bronchiolitis obliterans is a rare, serious lung disease in which the smallest airways, called bronchioles, become scarred and narrowed until they are partly or completely blocked. The nickname “popcorn lung” comes from a cluster of cases discovered in workers at microwave-popcorn factories in the early 2000s, but the disease has multiple causes ranging from chemical fumes and infections to organ transplant rejection. Once the scarring sets in, the damage is largely irreversible, which makes early recognition critical and prevention even more so.
How the Disease Got Its Nickname
In 2000, a Missouri state health department investigation turned up an unusual number of workers at a microwave-popcorn plant who had developed severe, fixed airway obstruction. A landmark study published in 2002 found that these workers had about 3.3 times the expected rate of airway obstruction overall, and among those who had never smoked, the rate was roughly 10.8 times what would be expected in a comparable group of people.1PubMed. Clinical Bronchiolitis Obliterans in Workers at a Microwave-Popcorn Plant Workers who handled the butter-flavoring mixtures directly had the highest rates of shortness of breath on exertion. The culprit was diacetyl, a naturally occurring chemical that gives butter its characteristic taste and smell, used in large quantities in the flavoring powders these workers inhaled daily.
The connection between cumulative diacetyl exposure and the severity of obstruction was strong enough for the researchers to conclude that these workers probably had occupational bronchiolitis obliterans caused by inhaling volatile butter-flavoring ingredients. The finding drew national attention and gave the disease a memorable, if slightly misleading, common name. “Popcorn lung” stuck in public consciousness, but the disease itself is not limited to popcorn workers and has been recognized in medical literature for decades under various other contexts.
What Actually Happens Inside the Lungs
Your airways branch like an upside-down tree, getting smaller with each split. The bronchioles are the tiniest branches, each only about a millimeter or less in diameter. In bronchiolitis obliterans, an injury triggers inflammation in and around these tiny tubes. As the body tries to heal, it lays down scar tissue (fibrosis) that thickens the walls of the bronchioles and gradually chokes them shut. This is called “constrictive” bronchiolitis because the scar tissue literally constricts the airway from the outside in.2PubMed. Inhalational Constrictive Bronchiolitis: The Evolution of our Understanding of this Disease
Unlike asthma, where airway narrowing is largely reversible with medications that relax smooth muscle, the narrowing in bronchiolitis obliterans is structural. The scar tissue does not relax when you use a bronchodilator inhaler. This is one of the key clinical clues: a patient whose breathing tests show obstruction that barely improves with inhaler use should prompt suspicion of something beyond garden-variety asthma.
Causes Beyond Popcorn Factories
Diacetyl inhalation may be the most famous trigger, but bronchiolitis obliterans has a surprisingly long list of causes. They fall into a few broad categories.
Chemical and Occupational Exposures
The earliest descriptions of this disease involved nitric acid spills and agricultural silo exposures, where workers inhaled nitrogen dioxide fumes from fermenting silage.2PubMed. Inhalational Constrictive Bronchiolitis: The Evolution of our Understanding of this Disease These events often followed a deceptive pattern: an acute exposure causing respiratory distress, a short-term improvement that seemed like recovery, and then a delayed progression to permanent lung damage. Diacetyl-related popcorn-worker cases followed a more gradual pattern of chronic exposure, but the end result under the microscope was the same. Military veterans exposed to burn pits in southwest Asia have also shown constrictive bronchiolitis on lung biopsies, with evidence of fibrosis and airway hyperresponsiveness in the majority of patients studied.3PubMed Central. Military burn pit exposure and airway disease: implications for our Veteran population
Post-Infection Cases
Certain respiratory infections, especially in young children, can trigger bronchiolitis obliterans as the healing process goes awry. Adenovirus is the most commonly implicated pathogen. A recent case series documented 11 children who developed post-infectious bronchiolitis obliterans after moderate to severe adenovirus-associated lower respiratory tract infections, with most requiring intensive respiratory support during the acute illness.4PubMed Central. Outbreak of Post‐Infectious Bronchiolitis Obliterans After Adenovirus Infection: A Case Series and Review of the Literature Other viruses like respiratory syncytial virus and influenza have been implicated in rarer cases. This post-infectious form is sometimes called PIBO (post-infectious bronchiolitis obliterans) and is predominantly a pediatric problem.
Transplant-Related Forms
Bronchiolitis obliterans is one of the most feared long-term complications of lung transplantation, where it represents a form of chronic rejection. The body’s immune system attacks the transplanted airways, eventually scarring them shut. This form is often referred to by its clinical counterpart, bronchiolitis obliterans syndrome (BOS), which is diagnosed by declining lung function rather than requiring a surgical biopsy.5PubMed Central. Bronchiolitis obliterans syndrome and restrictive allograft syndrome after lung transplantation: why are there two distinct forms of chronic lung allograft dysfunction? Bone marrow and stem cell transplant recipients can develop it too, as a manifestation of chronic graft-versus-host disease. In that setting, bronchiolitis obliterans is considered the only lung complication currently accepted as directly diagnostic of chronic graft-versus-host disease.6PubMed Central. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD
How Diacetyl Damages Airway Tissue
Research into the biological mechanism has focused on what diacetyl and related chemicals do to the cells lining the airways. Studies show that diacetyl can directly kill airway epithelial cells, damage proteins, and disrupt the normal balance of protein turnover inside cells.7PubMed. Flavorings-Related Lung Disease: A Brief Review and New Mechanistic Data With repeated exposure in animal models, this damage leads to airway fibrosis that closely resembles what is seen in human bronchiolitis obliterans.
The injury reaches deep into the airway’s repair machinery. Basal cells, which serve as the stem cells responsible for regenerating damaged airway lining, are particularly vulnerable. After diacetyl exposure, these basal cells show signs of protein damage and altered expression of key markers they need for renewal. The cell’s cleanup system, known as the ubiquitin-proteasome pathway, kicks in to try to clear damaged proteins, and when that repair system is blocked experimentally, the basal cell damage persists.8PubMed Central. Airway basal cell injury after acute diacetyl (2,3-butanedione) vapor exposure In plain terms, diacetyl not only kills airway cells but hobbles the cells responsible for regrowing them. Over time, scar tissue fills the gap instead of healthy new lining.
The Substitute Chemical Problem
After diacetyl was linked to popcorn lung, some manufacturers switched to alternative flavoring chemicals, most commonly 2,3-pentanedione. The hope was that these substitutes would be safer. The evidence suggests otherwise. In animal studies, rats inhaling 2,3-pentanedione developed airway damage comparable to that caused by diacetyl, including necrotizing inflammation of the trachea and bronchi.9PubMed Central. Respiratory and olfactory cytotoxicity of inhaled 2,3-pentanedione in Sprague-Dawley rats
A direct comparison study tested diacetyl, 2,3-pentanedione, and a longer-chain relative called 2,3-hexanedione head to head. At higher exposure levels, all five out of five rats exposed to diacetyl and all five out of five exposed to 2,3-pentanedione developed bronchial fibrosis. Even after a two-week recovery period, fibrosis persisted in every surviving animal in those groups. The longer-chain 2,3-hexanedione was less reactive and produced far less fibrosis, appearing in only two of twelve rats at the highest dose.10PubMed Central. Chemical Reactivity and Respiratory Toxicity of the α-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione The takeaway is that simply swapping one buttery-tasting chemical for a close cousin does not eliminate the hazard if the replacement is chemically similar enough to attack airway tissue in the same way.
E-Cigarettes and Vaping
The popcorn lung conversation resurfaced with the rise of e-cigarettes. Many flavored e-liquids contain diacetyl or 2,3-pentanedione as flavoring agents. A widely cited analysis of 51 flavored e-cigarette products found diacetyl in 39 of them and at least one of the three flavoring chemicals of concern in 47 of 51 products tested. These were not just candy and fruit flavors; “classic” and “menthol” varieties also contained them.11Environmental Health Perspectives. Flavoring Chemicals in E-Cigarettes: Diacetyl, 2,3-Pentanedione, and Acetoin in a Sample of 51 Products, Including Fruit-, Candy-, and Cocktail-Flavored E-Cigarettes
A separate evaluation of sweet-flavored e-liquids found diacetyl or its close relative acetyl propionyl in about three-quarters of samples tested. The median daily exposure for users was lower than what a factory worker might face, but roughly half of the products exposed consumers to levels above occupational safety limits set by the National Institute for Occupational Safety and Health (NIOSH).12Nicotine & Tobacco Research. Evaluation of Electronic Cigarette Liquids and Aerosol for the Presence of Selected Inhalation Toxins A risk assessment modeling diacetyl exposure among teen and adult e-cigarette users found that all estimated exposure scenarios produced hazard quotient values well above the threshold of concern, ranging from about 6 to nearly 300 times the safe benchmark dose.13PubMed. Risk assessment of inhaled diacetyl from electronic cigarette use among teens and adults
An important caveat: while these numbers indicate that the exposure risk is real, confirmed cases of bronchiolitis obliterans in individual vapers remain rare in the published literature. The disease takes time to develop and may be underdiagnosed, particularly among younger users who do not yet have a baseline health record for comparison. Whether widespread vaping will eventually produce a wave of popcorn lung cases the way factory work did is genuinely uncertain, but the chemical ingredients for it are clearly present in many products.
Why It Is Often Misdiagnosed
One of the most frustrating aspects of bronchiolitis obliterans is how easily it can be mistaken for more common conditions. Asthma and bronchiolitis obliterans share overlapping symptoms: chronic cough, wheezing, shortness of breath. Standard spirometry (breathing tests) in both conditions can show airflow obstruction. In children especially, this overlap leads to misdiagnosis; studies have documented that post-infectious bronchiolitis obliterans patients are frequently diagnosed with asthma first, sometimes for years, delaying appropriate evaluation and management.14European Respiratory Journal. Misdiagnosed asthma may mask the bronchiolitis obliterans
Even plain chest X-rays can appear normal in someone with bronchiolitis obliterans, which adds to the diagnostic challenge. The standard diagnostic workup relies on high-resolution CT scans of the chest, ideally with both inspiratory and expiratory images.15Journal of Occupational and Environmental Medicine. Constrictive Bronchiolitis Attributable to Inhalation of Toxic Agents: Considerations for a Case Definition The hallmark finding on CT is a “mosaic attenuation” pattern, where patches of lung appear lighter and darker side by side, reflecting areas that trap air next to areas that ventilate normally.16The Egyptian Journal of Radiology and Nuclear Medicine. Bronchiolitis Obliterans (BO): HRCT findings in 20 patients Other common CT findings include bronchiectasis (widened, damaged airways) and thickened bronchial walls.
Expiratory imaging, where the scan is taken while you breathe out, is particularly useful. In one study of lung transplant recipients, air trapping on expiratory CT had a sensitivity of 91% for detecting bronchiolitis obliterans, compared to just 36% for bronchiectasis on standard inspiratory images.17PubMed. Bronchiolitis obliterans after lung transplantation: detection using expiratory HRCT In at least one case, air trapping was visible on CT in a patient whose standard breathing tests were still normal, suggesting imaging can catch the disease before spirometry does. Surgical lung biopsy remains the definitive way to confirm the diagnosis, but it carries its own risks and is not always performed.
Treatment and Prognosis
There is no cure that reverses the scarring once it has occurred. Treatment focuses on slowing progression, managing symptoms, and addressing the underlying cause where possible. For transplant-related cases, adjusting immunosuppressive medications is the first step. For occupational cases, removing the person from the exposure is essential but does not undo existing damage.
Among pharmacological approaches, long-term azithromycin therapy has shown the most promise, particularly in transplant-related bronchiolitis obliterans syndrome. Azithromycin is technically an antibiotic, but it has anti-inflammatory properties that appear relevant here. Studies have shown it can meaningfully improve lung function in roughly 42% of patients with established BOS, while also reducing airway inflammation and the frequency of bacterial flare-ups.18PubMed. Lung transplantation: the role of azithromycin in the management of patients with bronchiolitis obliterans syndrome The exact mechanisms behind this benefit are still being worked out, and azithromycin does not help everyone.
For patients whose disease progresses despite treatment, lung transplantation becomes the last resort, though this carries the ironic risk of developing bronchiolitis obliterans again in the new lungs. Progression through the severity grades of BOS carries a steep mortality penalty: moving from a milder to a more severe grade roughly triples the risk of death at each step.19PubMed. Long-term survival after lung transplantation depends on development and severity of bronchiolitis obliterans syndrome
Occupational Safety and Regulation
The popcorn-factory outbreak was not entirely a surprise to everyone involved. Documents uncovered during litigation revealed that the flavoring industry’s trade organization had been aware of bronchiolitis obliterans cases in workers at butter-flavoring and popcorn plants but often failed to implement basic industrial hygiene improvements and, in some instances, actively concealed warning information. Multiple lawsuits resulted in large settlements for affected workers.
Regulatory response has been uneven. NIOSH issued recommended exposure limits for diacetyl and 2,3-pentanedione, but setting legally enforceable occupational exposure limits (OELs) has proven contentious. Different organizations have arrived at widely varying recommended limits, driven by disagreements over whether to base calculations on human or animal data and how much uncertainty to factor in when extrapolating from studies to real-world safety thresholds.20PubMed Central. Impacts of risk assessment data, assumptions, and methods: Considering the evidence for diacetyl and 2,3-pentanedione The result is that workers in different countries, and sometimes different states, may face very different levels of regulatory protection from the same chemical.
For e-cigarettes, the regulatory picture is even murkier. Some manufacturers have voluntarily removed diacetyl from their products, and some jurisdictions have restricted flavored e-cigarettes more broadly. But enforcement is spotty, and 2,3-pentanedione, the substitute that appears to be similarly dangerous, is not always covered by the same restrictions. Consumers who assume that a product labeled “diacetyl-free” is therefore safe from flavoring-related lung injury may be operating under a false sense of security.
When to Suspect Something Beyond Asthma
If you or someone you know has persistent cough and shortness of breath that does not improve with standard asthma treatment, and especially if there is a history of working with flavorings, industrial chemicals, or fumes, or a severe respiratory infection in childhood, bronchiolitis obliterans should be on the radar. The red flags are a poor response to bronchodilators, a history of relevant exposures, and progressive worsening over months to years rather than the episodic flare-and-recovery pattern typical of asthma.
Asking for a high-resolution CT scan with expiratory images is reasonable when the clinical picture does not add up. Standard chest X-rays miss the disease too often to be reassuring. Pulmonary function tests that show fixed obstruction, meaning the numbers barely budge after using an inhaler, are another important clue that distinguishes this from asthma or reversible airway disease. Early detection does not reverse the scarring, but it can lead to removal from the exposure source and initiation of treatments that may slow progression before severe, disabling damage accumulates.