Small Airway Involvement in Patients With Chronic Hypersensitivity Pneumonitis
Condition: Hypersensitivity Pneumonitis; Airway Disease Small
MeSH terms: Pneumonia; Alveolitis, Extrinsic Allergic; Hypersensitivity
Study type: Interventional

Summary: 
      Hypersensitivity pneumonitis (HP) is a syndrome with variable clinical presentation in which
      lung inflammation is caused by inhalation of specific organic antigens or low molecular
      weight particles in previously sensitized individuals. Systemic symptoms may or may not be
      present. Chronic HP represents the final stage of the disease, caused by prolonged exposure
      to a particular antigen, leading to pulmonary fibrosis. In chronic HP, pulmonary function
      tests (PFTs) commonly present a restrictive ventilatory pattern, with decreased diffusion of
      carbon monoxide (DLCO). Some patients can also have obstructive disorders with expiratory
      flow limitation, due to obstruction of the small airways typically caused by bronchiolar
      involvement in this pathology. However, PFTs are relatively insensitive for detecting small
      airway involvement when there is concomitant interstitial fibrosis. First, conventional PFTs
      may be normal in patients with small airway involvement, since they contribute to less than
      30% of the total airway resistance. In addition, damage to the small airways in HP is
      generally occurring parallel to areas of focal fibrosis - even when small airways are
      involved, these regions can be completely ignored, since they are excluded from ventilation.
      In summary, traditional PFTs are not sufficiently sensitive to detect diffuse small airway
      involvement in these diseases. In these cases, other functional tests, such as forced
      oscillation technique (FOT) and high resolution computer tomography (HRCT) scans of the chest
      with expired studies, could be used for this purpose.

      This will be a cross-sectional study, which will include the following evaluations in 28
      patients with HP recruited from our clinic:

      - Clinical variables: (A) demographic and anthropometric data; (B) Clinical data: Onset of
      symptoms and time of diagnosis

      C) Dyspnea score:

      D) Smoking: * Current or former smoker * Smoking history (number of cigarettes smoked per day
      and for how long);

        -  Spirometry with forced and slow maneuvers before and after bronchodilator (salbutamol);

        -  Plethysmography to measure lung volumes;

        -  Diffusion capacity of carbon monoxide (DLCO);

        -  High-resolution chest CT with expiratory scans;

        -  Six-minute walk test;

        -  Cardio-respiratory test using a maximal incremental treadmill.

        -  Forced oscillation technique (FOT).
    

Detailed description: 
      Hypersensitivity pneumonitis (HP) is a syndrome with variable clinical presentation, in which
      inflammation in lung parenchyma is caused by inhalation of organic antigens or specific low
      molecular weight substances in previously sensitized individuals. Systemic symptoms may or
      not be present. Chronic HP represents the final stage of this disease, where prolonged
      exposure to a particular antigen would lead to lung fibrosis. The list of new antigens is
      growing, but the main antigens responsible for this disease are exposure to mold and birds.

      Not all exposed individuals develop HP. The pathophysiology involves initial exposure and a
      subsequent decrease in antigen tolerance. Genetic susceptibility can also modulate the immune
      response to a specific antigen.

      There are no reliable epidemiological data on the incidence or prevalence of HP. Differences
      in the type of antigen sensitization, lack of standardized diagnostic criteria and
      underreporting are possible factors. In Mexico, one of the few population surveys showed an
      estimated incidence of 30 cases per 100000 inhabitants in 2 years (1988-1990); however, there
      are some bias that limit the extrapolation of data to other contexts.

      The patient rarely associates the onset of symptoms with a relevant exposure, making it
      important to actively search for environmental factors against respiratory complaints. It is
      believed that intermittent exposure to an antigen, long-term exposure to a small load of
      antigen or a cumulative effect of multiple episodes of acute exposure can cause chronic HP.
      It is noteworthy that only a small proportion of patients with a single episode of acute
      exposure will develop chronic HP.

      In chronic HP, the patient complains of dyspnea on exertion and dry cough. Systemic symptoms
      such as fever and weight loss are rarely reported and may be associated with episodes of
      acute exposure. Physical examination reveals crackles and less commonly, digital clubbing.
      Auscultation may reveal the presence of squawks arising from the abrupt opening of small
      airways. Hypoxemia is found in patients with more severe lung disease.

      The differential diagnosis with other fibrosing interstitial diseases is challenging, due to
      the overlap of clinical history, functional and tomographic findings in the terminal stages
      of these pathologies. There is no gold standard test for diagnosis of HP in all its forms:
      the diagnosis results in the combination of epidemiological, clinical, radiological data and
      other exams.

      High resolution computer tomography (HRCT) has a fundamental role in the differential
      diagnosis. However, in advanced stages, the tomographic scans can demonstrate a pattern
      indistinguishable from nonspecific interstitial pneumonia (NSIP) or usual interstitial
      pneumonia (UIP), with presence of architectural distortion, traction bronchiectasis and
      bronchiolectasis, minimum ground glass opacities and honeycombing. The interpretation of HRCT
      allows "clues" for the differential diagnosis with other idiopathic intersticial pneumonias
      (IIPs). In comparative HRCT studies, there were some findings showing small airway
      involvement, such as lobular areas with decreased attenuation and vascularity, air trapping
      and ground glass or centrilobular micronodules Surgical biopsy may aid in the differential
      diagnosis of HP from other chronic idiopathic interstitial pneumonitis, especially when
      exposure is unclear. Even in advanced fibrosis, the accentuation of inflammation around the
      small airways is the major finding.

      Pulmonary function tests (PFTs) commonly show restrictive ventilatory defect with decreased
      DLCO. There may be concomitant obstructive ventilatory defect, secondary to involvement of
      the small airways.

      However, PFTs are relatively insensitive for detecting small airway involvement when there is
      concomitant interstitial fibrosis. Firstly, conventional PFTs may be normal in patients with
      involvement of small airways since they contribute to less than 30% of total airway
      resistance. Furthermore, damage to small airways in HP is generally focal occurring in
      parallel with fibrosed areas - even when small airways are involved, these regions may be
      completely disregarded since they are excluded from ventilation, with PFTs globally featuring
      a standard restrictive pattern.

      In summary, traditional PFTs are not sensitive enough to detect diffuse small airway
      involvement in these diseases, no matter how severe it is, neither can detect focal changes.
      In these cases, the investigators hypothesize that other tests, such as forced oscillometry
      technique (FOT), with its experience widely recognized in the context of evaluation of
      obstructive diseases like asthma and chronic obstructive pulmonary disease (COPD) and the
      technique of negative expiratory pressure (NEP) could be used for this purpose. For now,
      imaging tests, especially high-resolution tomography with expiratory scans, seem to be more
      sensitive to detect small airway involvement.

      Removal of the causal exposure is the treatment of choice. The use of corticosteroids reduces
      the duration of the acute phase, but does not affect long-term prognosis. Inhaled
      corticosteroids and bronchodilators may be used when there is evidence of airflow limitation,
      but there is no evidence basing its use.

      2. Study hypothesis

      The investigators' hypothesis is that a proportion of patients diagnosed with chronic HP
      exhibit expiratory flow limitation, due to airway obstruction caused mostly by the
      bronchiolar involvement characteristic of this pathology. This involvement could be
      quantified through other functional tests, such as FOT, and imaging techniques such as high
      resolution CT scan of the chest with expiratory scans. This may be one of the mechanisms that
      justifies the lower exercise capacity and greater degree of dyspnea on exertion in these
      individuals, together with other factors secondary to interstitial lung fibrosis, even in
      those patients with normal FEV1 (forced expiratory volume in 1 second) /FVC (forced vital
      capacity) , FEV1, residual volume (RV) and resistance.
    

Intervention name(s): Salbutamol
Intervention type(s): Drug
Intervention description(s): Salbutamol after spirometry, plethysmography and forced oscillation technique.
Other intervention name(s): Aerolin
Intervention MeSH terms: Albuterol
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other