Hypersensitivity Pneumonitis: Epidemiology and Pathophysiology

00:00 Welcome back.

00:02 Today we're going to discuss hypersensitivity pneumonitis, a fascinating condition where the body's own immune system gets a little overzealous and attacks the lungs in response to something that's been inhaled.

00:14 So first let's define it.

00:16 Hypersensitivity pneumonitis is an immunologic lung syndrome triggered by an allergic reaction to inhaled agents, including organic antigens like those found in agricultural dusts and bioaerosols, or certain reactive chemicals.

00:30 It's important to remember that hypersensitivity pneumonitis isn't a single uniform disease.

00:36 Its intensity and how it presents can vary quite a bit.

00:41 Now let's start off by discussing its epidemiology.

00:46 The overall prevalence and incidence of hypersensitivity pneumonitis are thought to be relatively low.

00:52 However, a key takeaway is that these estimates vary considerably.

00:57 This variability stems from several factors, including a lack of internationally accepted diagnostic criteria, differences in seasonal and geographical exposure to inciting antigens, and various host factors.

01:11 So mild or subclinical cases of HP can often escape detection or be misdiagnosed as more common conditions like a viral illness or asthma.

01:19 Regarding who is most at risk, HP occurs more frequently in certain occupational groups and among individuals with specific hobbies due to targeted exposures.

01:31 For example, farmers and pigeon breeders are classic examples of populations with higher reported prevalence rates due to their consistent exposure to causative antigens.

01:40 Globally, bird-related HP is the most commonly reported form.

01:45 Demographically, HP is noted more often in middle-aged men and its prevalence tends to increase with age.

01:51 Finally, prolonged exposure to organic dusts and endotoxins in occupational settings has been shown to greatly increase the risk of developing HP.

02:01 Okay, let's now talk about the pathophysiology and etiology of this condition.

02:06 Hypersensitivity pneumonitis can be triggered by a vast array of airborne antigens with over 300 different causes identified.

02:15 Let's touch upon a few prominent examples to illustrate this diversity.

02:20 Perhaps one of the most well-known is farmer's lung, which results from inhaling thermophilic actinamide seeds found in moldy hay or vegetable matter.

02:29 Another common example is bird fancier's lung.

02:31 This affects individuals exposed to proteins present in the feathers and droppings of birds like pigeons, parakeets, and chickens.

02:39 The condition isn't limited to agricultural or animal exposures.

02:44 For instance, chemical workers' lung can develop from exposure to various industrial agents such as isocyanates.

02:49 And even indoor environments can pose a risk, as seen with humidifier fever caused by antigens like fungi from contaminated air conditioning and humidifying systems.

03:01 These are just a few examples from a comprehensive list.

03:04 To explore the full range of diseases, their specific exposures, and the antigens involved, we encourage you to download the supplementary materials accompanying this presentation.

03:15 There, you can take a closer look at the complete table at your own pace.

03:20 Now regarding the pathogenesis, when an individual inhales these antigenic particles, the first line of defense, the innate immune system, is triggered.

03:30 Specialized immune cells called antigen-presenting cells or APCs, mainly macrophages and dendritic cells residing in the lungs, are activated.

03:37 Once activated, the dendritic cells take a crucial next step.

03:42 They travel from the lungs to nearby lymph nodes.

03:46 Here, they present the inhaled antigen to T-cells via the HLA-CD4 complex, thereby kick-starting the adaptive immune response.

03:57 Now activated macrophages and T-cells release a variety of powerful chemical signals.

04:03 These include pro-inflammatory cytokines and chemotactic factors, which keep attracting immune cells, key signals such as interleukins, interferon gamma, and tumor necrosis factor.

04:14 All of this leads to a fairly aggressive immune response that will be reflected in a variety of symptoms like fever, cough, and general malaise that we'll discuss shortly.

04:23 All of this promotes granuloma formation, where activated macrophages and other immune cells cluster together.

04:31 This condition may resolve without major complications.

04:34 However, in some individuals, particularly with continued exposures, the repeated inflammatory insults transition into a chronic fibrotic process.

04:45 This damaging progression is often marked by a switch in the T-cell response from the initial Th1 type to a Th2 type.

04:52 The Th2 response brings with it a different set of cytokines.

04:57 These Th2 cytokines then promote fibrosis by stimulating fibroblasts to proliferate and produce more connective tissue.

05:04 Persistent inflammation in the lung tissue leads to ongoing damage to the delicate lung structures, and repeated bouts of inflammation will cause interstitial fibrosis, resulting in tissue stiffness, decreased capacity for gas exchange, and consequently low oxygen levels.