T2-low asthma

Understanding T2-Low Asthma

T2-low asthma, also known as Type 2 low asthma, is a subtype of asthma characterized by limited airway inflammation and a distinct set of clinical features.

• Severe disease: T2-low asthma is often a severe disease that can be poorly or non-responsive to corticosteroids even at high doses [5].
• Limited treatment options: Unlike other forms of asthma, biologic therapeutics are lacking for T2-low asthma, making it challenging to manage [2].
• Paucigranulocytic asthma: This subtype is characterized by a low number of granulocytes (a type of white blood cell) in the airways [3].
• Neutrophilic asthma: Another form of T2-low asthma is neutrophilic asthma, which is marked by an increased presence of neutrophils (a type of white blood cell) in the sputum [7].

Key characteristics

• Eosinophilic airway inflammation: While eosinophils are typically associated with T2-high asthma, they can also be present in T2-low asthma, although at lower levels [4].
• Upregulation of T2 immune pathways: Patients with type 2 (T2)-“high” asthma have upregulated T2 immune pathways, including IL-4 and IL-13 gene sets, which may also be present in some cases of T2-low asthma [6].

Patient profile

• Older adults: T2-low asthma is often associated with older adults who are overweight or obese [9].
• Heavy smokers: Smoking can contribute to the development of T2-low asthma by leading to air trapping and other respiratory complications.

Overall, T2-low asthma is a complex and challenging condition that requires careful management and treatment.

Common symptoms of Type 2 (T2)-low asthma include:

• Frequent coughing, especially at night [3]
• Shortness of breath, even during mild activity or at rest [3]
• Wheezing [3]

Additionally, research suggests that T2-low asthma is associated with obesity and increased systemic IL-6 inflammation [2]. This can lead to a range of symptoms, including:

• Weight-related issues
• Metabolic dysfunction

It's essential to note that these symptoms may not be as pronounced in individuals with T2-low asthma compared to those with other types of asthma. However, they can still significantly impact daily life and overall health.

References:

[1] Potential mechanisms of T2 low asthma include the following: (1) non-T2 inflammation within the lung (airway neutrophilia, type 1 [T1] [IFN-mediated] or type 3 [IL-17–mediated] immune pathways), (2) systemic inflammation associated with IL-6, obesity, and metabolic dysfunction, and (3) noninflammatory (paucigranulocytic) mechanisms ...

[2] Type-2 low asthma is associated with obesity[55], perhaps related to increased systemic IL-6 inflammation[110].

[3] What are symptoms of Type 2 inflammation in asthma? · Frequent coughing, especially at night · Shortness of breath, even during mild activity or at rest · Wheezing ...

Note: The information provided is based on the search results and may not be an exhaustive list of all possible symptoms. If you have specific concerns or questions, it's always best to consult a healthcare professional for personalized advice.

Diagnostic Approach to T2-Low Asthma

T2-low asthma, also known as non-eosinophilic asthma, is a subtype of asthma characterized by the absence or low levels of type 2 inflammatory biomarkers. The diagnostic approach to this condition involves several steps:

• Clinical evaluation: Patients with suspected T2-low asthma should undergo a thorough clinical evaluation, including a detailed medical history and physical examination [3].
• Spirometry: Spirometry is a crucial diagnostic tool for assessing lung function in patients with asthma. In T2-low asthma, spirometric values may be within the normal range or show mild airflow limitation [7].
• Fractional exhaled nitric oxide (FeNO): FeNO levels are typically low in patients with T2-low asthma, as this biomarker is associated with type 2 inflammation [3][7].
• Blood tests: Blood tests may be performed to rule out other conditions that can mimic T2-low asthma. These tests may include complete blood counts, liver function tests, and measurements of inflammatory markers such as C-reactive protein [9].

Current Challenges in Diagnosing T2-Low Asthma

Despite the availability of these diagnostic tools, there are still challenges in accurately diagnosing T2-low asthma. One major limitation is the lack of specific biomarkers for this condition. While FeNO levels may be low in patients with T2-low asthma, they can also be normal or elevated in some cases [4].

Future Directions

Research is ongoing to identify more accurate and reliable diagnostic markers for T2-low asthma. For example, studies have investigated the potential of tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), as a therapeutic agent in this condition [5][8].

References

[3] K Samitas · 2017 · Cited by 110 — This review aims to discuss the diagnostic approach to T2-low asthma characterized by noneosinophilic airway inflammation and consider older as well as more recent studies.

[4] C Kyriakopoulos · 2021 · Cited by 72 — Although much progress has been made in elucidating T2-high inflammation pathways, no specific biomarkers for T2-low asthma have been identified.

[7] AM Fitzpatrick · 2020 · Cited by 135 — Patients with type 2 (T2)-“high” asthma are characterized by upregulation of T2 immune pathways (ie, IL-4 and IL-13 gene sets) and eosinophilic airway inflammation.

[8] TSC Hinks · 2021 · Cited by 138 — In a phase 2 RCT, treatment with subcutaneous tezepelumab, a human anti-TSLP monoclonal antibody, reduced asthma exacerbations by 60–70% and improved lung function in patients with severe asthma.

[9] AM Fitzpatrick · 2020 · Cited by 135 — This review details definitions and clinical features of T2-“low” asthma, potential mechanisms and metabolic aspects, pediatric considerations, and potential therapeutic options.

Treatment Options for T2-Low Asthma

T2-low asthma, also known as non-eosinophilic asthma, is a subtype of asthma that is characterized by low levels of type 2 inflammatory biomarkers. This condition can be challenging to treat, but various drug treatments have been explored.

• Biologics: Biologic medications, such as mepolizumab and reslizumab, have shown promise in treating T2-low asthma. These drugs target specific proteins involved in the inflammation process [8][9].
• Azithromycin: Azithromycin, an antibiotic, has been found to improve symptoms and reduce exacerbations in patients with T2-low asthma [7].
• Bronchial Thermoplasty (BT): BT is a minimally invasive procedure that can help reduce airway constriction and improve lung function in severe uncontrolled asthma, including T2-low asthma [4].
• Asthegolimab: Astegolimab, an anti-IL-33 monoclonal antibody, has been shown to decrease exacerbations in patients with T2-low asthma [6].

Limitations of Current Treatments

While these treatments have shown promise, there is still a need for more effective and targeted therapies for T2-low asthma. Many patients do not respond well to standard treatments, such as corticosteroids and bronchodilators.

• Limited treatment options: Patients with T2-low asthma often have limited treatment options, making it essential to explore new and innovative approaches [5][9].
• Need for comprehensive assessment: A comprehensive assessment of T2 status is crucial in guiding treatment decisions for patients with difficult-to-treat and severe asthma [10].

Future Directions

Further research is needed to develop more effective treatments for T2-low asthma. This may involve exploring new biologic medications, improving existing therapies, or developing novel approaches that target specific aspects of the disease.

References:

[4] Innovative treatments (bronchial thermoplasty, BT) have been used recently as therapy for severe uncontrolled asthma, such as paucigranulocytic. [5] Patients with asthma and low levels of type 2 inflammatory biomarkers (T2 low) have limited effective treatment options. Such ... [6] Astegolimab, administered subcutaneously every 4 weeks at the dose of 70 mg or 490 mg (but not 210 mg), is able to decrease exacerbations, in ... [7] Multiple available interventions target these characteristics, including standard inhalers, azithromycin, and lifestyle interventions of weight loss and smoking ... [8] T2-low asthma is a problem urgently needing solution: These patients have poor response to steroids, which combined with bronchodilators, are the cornerstone of ... [9] T2-low asthma is an often severe asthma subtype with limited treatment options and biologic therapeutics are lacking. [10] This study emphasizes the need to undertake a comprehensive assessment of T2 status in difficult-to-treat and severe asthma to guide treatment ...

Differential Diagnosis of T2-Low Asthma

T2-low asthma, also known as non-allergic or paucigranulocytic asthma, is a subtype of asthma that presents with low levels of T2 inflammation. The differential diagnosis for T2-low asthma involves ruling out other conditions that may present with similar symptoms.

Key Features to Consider:

• Lack of prominent T2 inflammation: T2-low asthma is characterized by the absence or low levels of T2 immune pathways, such as IL-4 and IL-13 gene sets.
• Eosinophilic airway inflammation: Patients with type 2 (T2)-“high” asthma have upregulation of T2 immune pathways and eosinophilic airway inflammation, which is not present in T2-low asthma.
• Resistant to inhaled corticosteroids: T2-low asthma tends to be more resistant to inhaled corticosteroids compared to T2-high asthma.

Differential Diagnosis:

• T2-high asthma: This subtype of asthma presents with upregulation of T2 immune pathways and eosinophilic airway inflammation, making it a key differential diagnosis for T2-low asthma.
• Paucigranulocytic asthma: This condition is characterized by low levels of granulocytes in the airways and can be further defined as Type 1 or Type 2 paucigranulocytic asthma.
• Non-allergic asthma: This subtype of asthma presents with symptoms similar to T2-low asthma but without the presence of T2 inflammation.

Diagnostic Approaches:

• Exhaled and blood biomarkers: Sputum transcriptomics, exhaled nitric oxide (FeNO), and blood biomarkers can be used to differentiate between T2-high and T2-low asthma.
• Sputum analysis: Sputum analysis can help identify the presence or absence of granulocytes in the airways.

References:

• [1] F Peri · 2023 · Cited by 14 — T2-high asthma is classified as allergic and non-allergic, whereas T2-low asthma can be further defined as paucigranulocytic asthma, Type 1 and ...
• [3] by C Kyriakopoulos · 2021 · Cited by 72 — T2-low asthma presents with either neutrophilic or paucigranulocytic inflammation, tends to be more resistant to inhaled corticosteroids, and it involves ...
• [5] by TF Carr · 2021 · Cited by 11 — T2 low asthma is defined by the lack of prominent T2 inflammation and can be defined by exhaled and blood biomarkers, sputum tran- scriptomics, or sputum ...