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Exhaled NO in diffuse alveolar haemorrhage
  1. G Rolla1,
  2. E Heffler1,
  3. G Guida1,
  4. R Bergia1,
  5. C Bucca2
  1. 1Allergologia e Immunologia Clinica, Ospedale Mauriziano Umberto I and Dipartimento di Scienze Biomediche e Oncologia Umana, University of Torino, Italy
  2. 2Ospedale Molinette and Dipartimento di Scienze Biomediche e Oncologia Umana, University of Torino, Italy
  1. Correspondence to:
    Dr G Rolla
    Allergologia e Immunologia Clinica, Ospedale Mauriziano, Largo Turati 62, 10128 Torino, Italy;

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The syndrome of diffuse alveolar haemorrhage (DAH) is associated with a wide variety of diseases. Haemoptysis, falling haemoglobin, and air space opacities on the chest radiograph constitute a triad of features suggestive of DAH which should be confirmed by bronchoalveolar lavage (BAL).1 However, haemoptysis can be absent in up to one third of patients. A sensitive marker of DAH is a sequential increase in the carbon monoxide lung transfer factor (Tlco). This results from the increased availability of haemoglobin within the alveolar compartment which avidly binds carbon monoxide.2 Although informative, the Tlco often cannot be measured in patients with DAH as they might be too ill. Nitric oxide (NO) combines with haemoglobin much faster than carbon monoxide and is continuously produced in the respiratory tract. Exhaled NO can be measured either online or offline even in acutely ill patients by collection of exhalate in a bag for subsequent analysis.3 We reasoned that DAH could be associated with low levels of exhaled NO because of the increased availability of haemoglobin within the alveolar compartment binding NO.

A 52 year old non-smoking man with a history of allergic rhinitis and asthma was admitted with increasing dyspnoea. His asthma had been controlled by maintenance inhalation of salmeterol and fluticasone. In the previous 3 weeks the patient had experienced painful paraesthesias. On admission he was in mild respiratory distress with a peak expiratory flow rate of 415 l/min (92% of his personal best value), arterial oxygen tension (Pao2) 8.6 kPa (65 mm Hg), haemoglobin 11 g/dl, and WBC 23 000 (eosinophils 23%). Exhaled air was collected in a sample bag according to American Thoracic Society recommendations (inspiratory air NO concentration <5 ppb, expiratory flow rate 350 ml/s)3 and NO was measured within 2 hours of collection using a chemiluminescent analyser (NIOX, Aerocrine, Solna, Sweden). The initial level of exhaled NO was 4 ppb (normal reference value in our laboratory is 12 (2) ppb). Twelve hours later the haemoglobin fell to 9.1 g/dl, Pao2 was 7.2 kPa (54 mm Hg), and confluent air space opacities were apparent on the chest radiograph (fig 1). The exhaled NO level had fallen to 2 ppb and BAL confirmed the diagnosis of DAH and excluded infection. Antineutrophil cytoplasm antibodies were reported to be present with a high titre of antibodies against myeloperoxidase. Sensory motor mononeuritis multiplex was diagnosed by electromyographic and nerve conduction studies. The patient fulfilled the criteria for the diagnosis of Churg-Strauss syndrome (CSS) and was treated with intravenous pulse methylprednisolone 1 g for 3 days followed by oral prednisone 1 mg/kg and cyclophosphamide 2 mg/kg/day. His clinical condition and oxygenation rapidly improved, together with progressive clearing of the chest radiograph. Exhaled NO levels measured 2, 5 and 8 days after the diagnostic BAL rose to 5, 9 and 15 ppb, respectively.

Figure 1

 Chest radiograph showing bilateral air space opacities at a time when a very low level of NO was measured in the exhaled air.

CSS is an uncommon systemic vasculitis which involves the small blood vessels of the lungs, peripheral nerves, skin and, less frequently, the heart and gastrointestinal tract. The most frequently encountered chest radiographic pattern in CSS is ill defined infiltrates, often peripheral, which may simulate eosinophilic pneumonia.4 Alveolar haemorrhage occurs infrequently in CSS, while it has been reported in as many as one third of patients with microscopic polyangiitis. When a diagnosis of DAH is being considered, this case shows the potential diagnostic aid of measuring exhaled NO. The sequential measurements of exhaled NO showed a progressive increase, starting from a very low value, which correlated well with the clinical and radiographic improvement of the patient. It is interesting that, in acute pneumonia (which should be considered in the differential diagnosis), exhaled NO levels have been reported to be high, at least in the one published case series.5


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  • Affiliated to the Italian Nitric Oxide Club.

    Supported by a grant (ex 60%) from the Ministero Italiano dell’Università e della Ricerca Scientifica.

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