O2 saturation normal but short of breath

Each year, between 25% and 50% of people in the U.S. see a doctor for shortness of breath. You may have felt it, too -- the uncomfortable feeling you get when you can't seem to get enough air.

It’s a common symptom, and one that's usually harmless -- the result of a tough workout or a stressful day. But it can also be a sign that you have another health problem, such as anxiety, a lung infection like pneumonia, asthma, or heart disease.

How do you find out what’s going on? Your doctor can do some basic tests to help you get to the bottom of your shortness of breath.

When Should I See a Doctor?

If shortness of breath keeps you from doing your regular daily activities, that’s reason enough to call the doctor. But definitely schedule an appointment if you have trouble breathing along with any of these symptoms:

  • Shortness of breath when you’re resting or lying down
  • Fever, chills, night sweats
  • Fast, fluttering heartbeats
  • Wheezing

Tests to Diagnose Shortness of Breath

At your appointment, your doctor will ask a few questions about your medical history and do a physical exam. This might include listening to your heart and lungs for signs of congestion, murmur, or anything else unusual.

The results of the exam may lead them to order a few tests to help figure out what else might be causing your breathing problems.

Chest X-ray. It can show the doctor signs of conditions such as pneumonia or other heart and lung problems. It’s painless and easy -- a radiology technologist can do one in about 15 minutes.

Oxygen test. Also called pulse oximetry, this helps your doctor measure how much oxygen is in your blood. They’ll place a clothespin-like sensor on your finger, which uses light to detect oxygen. Other than the pressure of the sensor, you won’t feel anything.

Electrocardiography (EKG). You might get this test in your doctor’s office or a hospital. A technician will attach small electrodes to your chest with gel or tape, and a machine will measure the electrical impulses that make your heart beat. An EKG can show your doctor if blood flow to the heart is impaired.

Lung function test. This measures how well your lungs work and lets your doctor know if something is blocking or keeping them from using air properly. It can also show how well your lungs can transport and use oxygen. One type of lung function test is called spirometry. You breathe into a mouthpiece that connects to a machine and measures your lung capacity and air flow. Your doctor may also have you stand in a box that looks like a telephone booth to check your lung capacity. This is called plethysmography. Each of these tests helps your doctor diagnose problems such as asthma, emphysema, or COPD.

Blood test. A doctor or nurse will use a needle to take blood from a vein in your arm and send it to a lab for tests. The results can tell them whether or not conditions such as anemia or heart failure are making you short of breath.

If your shortness of breath is severe or comes with other symptoms such as confusion, chest pain, jaw pain, or pain down your arm, call 911 right away.

History

At the age of 30, a young father noticed a low oxygen saturation while playing with the finger pulse oximeter of his child awaiting surgery. Since he was completely asymptomatic, he did not seek medical attention. At the age of 51, he was referred to the outpatient clinic of our pulmonary department after detection of a severe nocturnal “hypoxemia”. Previous evaluation for obstructive sleep apnea by nocturnal respiratory polygraphy because of snoring revealed a significantly decreased average oxygen saturation (SpO2 71%). The former smoker (25 pack-years) was known for allergic/seasonal bronchial asthma with occasional use of an inhaled short-acting β-2-selective adrenergic agonist (terbutalin) preceding physical activity. He denied having respiratory symptoms like dyspnea, cough, thoracic pain, or infections, and did not experience a decline of his physical performance.

The patient presented to our outpatient clinic with a significantly decreased peripheral O2 saturation of 76-82% while breathing ambient air, which was measured by different pulse oximeters (Fig. 1). SpO2 rose only to 86% while breathing 7 L/min supplemental oxygen via nasal cannula. Other vital signs were normal (blood pressure 124/68 mm Hg, heart rate 86 beats/min, respiratory rate 16/min) and the patient showed no signs of respiratory distress. Physical examination revealed normal breath sounds without any signs of heart failure. Skin coloration was inconspicuous. Pulmonary function tests showed normal lung volumes without restriction (TLC 6.06 L, 89% predicted) or airway obstruction (FEV1/FVC 75%, FEV1 3.16 L, 89% predicted), but signs of small airway disease (MEF50 66% predicted). The diffusing capacity was above normal range (DLCO 126% predicted). Spiroergometry confirmed a normal cardiopulmonary performance (VO2max 23.5 mL/min/kg, 95% predicted) with a mildly diminished oxygen pulse (19.6 mL, 76% predicted), decreased slope and early plateau. Arterial blood gas analysis measured an oxygen saturation (SaO2) of 89%, paO2 10.9 kPa (82 mm Hg) and p50 5.3 kPa (40 mm Hg). Table 1 lists the laboratory results.

Table 1

Results of pulse oximetry, arterial blood gas analysis and further laboratory analyses

Fig. 1

51-year-old asymptomatic male. Patient with unremarkable appearance (no cyanosis, no jaundice). Low SpO2 (73%/79%) measured with two different pulse oximeters.

What is your diagnosis?

Diagnosis: Hemoglobinopathy Cheverly

Due to the discrepancy between invasively and noninvasively measured SO2, evaluation for an abnormal hemoglobin was performed. Conventional hemoglobin electrophoresis (alkaline cellulose acetate) was normal. Alpha-2 hemoglobin [3.2% (normal range 1.8-3.2%)] and fetal hemoglobin [0.5% (normal range <1.5%)] were not increased. High-pressure liquid chromatography showed a small peak at 4.52 min (Fig. 2) leading to the suspicion of Hb Constant Spring, the most common nondeletional α-thalassemia [1]. However, performing Sanger sequencing of the α-globin gene cluster, neither Hb Constant Spring nor any other point mutation could be detected.

Fig. 2

Cation-exchange high-pressure liquid chromatogram of the patient's blood sample showing an abnormal peak after 4.52 min retention time (arrow).

The oxygen saturation curve assessed by spectrophotometer (Fig. 3) confirmed the elevated p50 (4.4 kPa/32.7 mm Hg), which indicates a reduced oxygen affinity of the hemoglobin. Finally, by sequencing the β-globin gene (Fig. 4), a heterozygous mutation c.137 T>C, previously described as hemoglobin Cheverly, was detected.

Fig. 3

Oxygen dissociation curves of normal (healthy donor, green) and low oxygen affinity (patient, blue) hemoglobin measured by dual wavelength spectrophotometer (HemoAnalyzer®, TCS Medical Products, USA). As the p50 value increases (blue curve), the oxygen affinity of hemoglobin decreases (right shift) compared to the healthy donor (green curve).

Fig. 4

Sanger sequencing of the β-globin gene cluster. This cutout of the β-globin gene Sanger sequencing of the index patient illustrates the detected base substitution (T>C, indicated by Y) at position codon 137 (highlighted with a box). The reference sequence (HBB) is shown at the top and the four DNA bases (T, C, A, G) are represented by different colors. Further, the location of the mutation in the β-globin gene cluster is illustrated by the boxes above the sequences showing part of intron 1 and 2 as well as exon 2, where the described mutation is indicated with a red bar.

Discussion

Impairment in gas exchange or ventilation/perfusion mismatches are the most common causes of low SpO2 in daily routine in pulmonary medicine. Potential sources of error in pulse oximetry are poor peripheral perfusion, skin pigmentation, nail polish, motion artefacts and interfering ambient light. Although anemia does not change the ratio of oxyhemoglobin to deoxyhemoglobin, severe anemia can cause underestimation of SpO2, especially in hypoxemic subjects, mainly because pulse oximeters are calibrated on healthy subjects without anemia [2,3]. In general, small amounts of COHb and MetHb are not detected by pulse oximetry and lead to overestimation of SpO2, if present [4]. Variant hemoglobins are rare causes of falsely low pulse oximetry readings and are usually taken into consideration only after extensive assessment for respiratory and cardiac diseases, exclusion of MetHb, SulfHb, COHb, and other factors disturbing the performance of pulse oximeters [5].

The true SaO2 is measured by arterial blood gas analysis (applying more than 100 wavelengths). Discordant SaO2 and SpO2 values (defined as >5% difference) occur in some variant hemoglobins, with underestimation of the true SaO2 because these hemoglobins have unusual absorption spectra for which the two wave pulse oximeters are not designed [6]. If SaO2 and SpO2 are concordantly low (<5% difference), focus should be on the amount of oxygen dissolved in arterial blood (paO2). Physiologically, the oxygen saturation increases in an S-shaped curve as paO2 rises. This curve can shift to the right with increase in temperature, lower pH (acidity) and higher concentrations of CO2 or 2,3-bisphosphoglycerate [7]. An increased p50 indicates a shift of the curve to the right and towards lower oxygen affinity, which enables the hemoglobin to unload more oxygen in the peripheral tissues. Therefore, at normal paO2, the tissue oxygenation of hemoglobin Cheverly is not affected, despite a lowered SaO2.

Hemoglobinopathies are common hereditary diseases and more than 1,000 mutations of the globin chains are described. The quantitative thalassemia syndromes are the most frequent mutations and prevalence can be as high as 95% in certain populations. Most of the qualitative hemoglobinopathies have frequencies below 1% and can be associated with various or even no clinical manifestations [8]. In 1982 and 1983, an elderly Italian male with cyanotic heart disease [9] and an anemic female in Baltimore [10] were the first patients described with the Cheverly variant hemoglobin. In a German observational study, over a period of four decades, only 9 patients within hemoglobin Cheverly have been found [11]. A point mutation in the β-globin gene (single base modification) with replacement of thymidin by cytosin (c.137 T>C) and consecutive replacement of the amino acid phenylalanine by serine (p.45 Phe>Ser) weakens the heme-globin interaction and can cause instability of the affected β-globin chain. This can cause a mild hemolytic anemia in some of the cases. The low oxygen affinity of hemoglobin Cheverly causes the slightly decreased SaO2 in the presence of a normal paO2 measurement. In addition, the abnormal absorption spectrum of hemoglobin Cheverly explains the discordantly lower SpO2 compared with SaO2 [12,13].

Conclusion and Clinical Implications

In rare cases, a variant hemoglobin can be the reason for falsely low SpO2 readings and has to be considered in patients without any cardiopulmonary symptoms. Examination by electrophoresis and high-pressure liquid chromatography might not be sufficient to detect hemoglobinopathy, and sequencing of the globin genes might be necessary. Variant hemoglobins that have an abnormal absorption spectrum should be suspected if SpO2 and SaO2 are discordant. Low-affinity hemoglobin is present if p50 is elevated. In the case of hemoglobin Cheverly, both factors contribute to the abnormal constellation of decreased SaO2 and SpO2. Hemoglobin Cheverly is not expected to cause symptoms, but counselling of the affected individuals and equipping them with emergency cards can avoid unnecessary diagnostic and therapeutic procedures in case of routine medical interventions or medical emergencies, where the attending physician has to know about the inaccurate pulse oximeter reading. Further, we suggest a screening of family members simply by measuring SpO2 with a pulse oximeter.

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Can you have shortness of breath with normal oxygen levels?

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